PROTECT

Background

Each year, approximately 300 to 400 women are diagnosed with locally advanced cervical cancer in the Netherlands. The treatment combines external beam radiation therapy with concurrent chemotherapy, followed by brachytherapy, and is very effective. However, the majority of women experience treatment-related side effects, involving the gastrointestinal and urogenital tracts and the immune system. Compared to the standard photon therapy, proton therapy reduces dose to organs around the tumor and might decrease side effects. However, clinical studies evaluating proton therapy in locally advanced cervical cancer are not yet available.

Objective

The PROTECT study is a non-randomized, prospective, multicenter phase-II trial comparing proton therapy with photon therapy for locally advanced cervical cancer. Additionally, bone marrow sparing capability of both techniques is evaluated. The study allows for the development and implementation of proton therapy for this patient group and will assess dosimetric and clinical outcomes, safety, tolerability, and quality-of-life. Additionally, the effect on the immune system will be evaluated using water-fat MR scans of the bone marrow, blood samples, and an additional tumor biopsy.

Study population and sample size

Adult patients with a histological diagnosis of locally advanced cervical cancer with pelvic and/or para-aortic lymph node involvement and an indication for curative primary chemoradiotherapy are eligible.

In the first phase of the study, 15 patients have been enrolled in the photon therapy group. In the second phase of the study, 15 patients will be enrolled in the proton therapy group.

Treatment

All patients will be treated with 45 Gy/25 fractions photon or proton external beam radiation therapy, concurrent cisplatin, followed by brachytherapy. External beam radiation therapy will include bone marrow sparing. Patients in the proton therapy group will travel to HollandPTC for the external beam radiation therapy.

Monitoring

Patients will be followed for up to twelve months after treatment with quality-of-life questionnaires, one additional tumor biopsy during brachytherapy application, blood samples, and water-fat MR scans. The majority of the measurements is integrated in the standard clinical routine.

Endpoints

The primary endpoint will be to evaluate whether proton therapy can reduce the mean dose of the pelvic bones and the volume of the bowel receiving 15 Gy (V15Gy) in clinical practice, compared to photon therapy. Secondary endpoints include the comparison between proton therapy and photon therapy with respect to dosimetric parameters, clinical outcomes, health-related quality of life, safety and tolerability. Furthermore, the effect proton therapy and bone marrow sparing on the local and systemic immune system will be evaluated using water-fat MR scans of the bone marrow, blood samples, and an additional tumor biopsy.

This study is partly funded by Varian Medical Systems, Inc., a Siemens Healthineers Company.

• Leiden University Medical Center, Leiden, The Netherlands
• Holland Proton Therapy Center, Delft, The Netherlands

PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System. Corbeau, A.; Nout, R.A.; Mens, J.W.M.; Horeweg, N.; Godart, J.; Kerkhof, E.M.; Kuipers, S.C.; van Poelgeest, M.I.E.; Kroep, J.R.; Boere, I.A. et al. (2021) Cancers. 13(20), 5179

Margin and robustness settings for a library-of-plans IMPT strategy for locally advanced cervical cancer. Kuipers, S.C.; Godart, J; Negenman, E.M.; Corbeau, A.; Zolnay, A.G.; Deuzeman, H.H.; de Boer, S.M.; Nout, R.A.; Hoogeman, M.S. (2024) Physics in Medicine & Biology. 69(24), 245016 

Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer. Kuipers, S.C.; Godart, J.; Corbeau, A.; Breedveld, S.; Mens, J.W.M.; de Boer, S.M.; Nout, R.A.; Hoogeman, M.S. (2024) Radiotherapy and Oncology. 195.

Erasmus Medical Center, Rotterdam

Remi Nout
Jeremy Godart
Jan Willem Mens
Henrike Westerveld
Mischa Hoogeman
René Vernhout

Leiden University Medical Center, Leiden (sponsor)

Stephanie de Boer (principal investigator)

Carien Creutzberg
Anouk Corbeau

Holland Proton Therapy Center, Delft

Jeremy Godart
Eva Negenman
Mischa Hoogeman