PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System

Abstract

External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

Health-related quality of life and patient-reported symptoms after postoperative proton beam radiotherapy of cervical and endometrial cancer: 2-year results of the prospective phase II APROVE-trial

“…However, dose reductions may not necessarily result in clinically observed improvements in the appearance of symptoms or HRQOL and further investigations to determine which gynecologic tumor patients might profit in clinical routine from gastrointestinal toxicity and hematotoxicity reduction from proton beam radiotherapy are urgently needed. In this context, the primary objective of the PROTECT trial [ 47 ] will further compare intensity-modulated photon therapy to proton beam therapy for 15 women in each treatment arm for locally advanced cervical cancer in combination with chemotherapy in the definitive setting and will analyze dosages to organs at risk for pelvic bones and the bowel. But recruitment of this prospective phase II trial is still ongoing and results are pending.…”

The impact of bone marrow sparing on organs at risk dose for cervical cancer: a Pareto front analysis

“…While we investigated Pareto fronts for the sparing of the PB for the treatment of cervical cancer with VMAT, the technique is also applicable for other tumor sites, OAR, and treatment modalities. With the same methodology of BMS, future studies can investigate the possibilities of BMS for proton therapy ( 32 ).…”

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density

“…Future interests could concern proton therapy which is currently the subject of a Phase-II-Trial [33] . This study evaluate the differences in toxicities between photon therapy and proton therapy, both combined with chemotherapy for locally advanced CC, and could provide new data on PIFs incidence.…”