ESTRO 2024 - Abstract Book

S267

Brachytherapy - Gynaecology

ESTRO 2024

1 Gustave Roussy Cancer Campus, Radiation Oncology, Villejuif, France. 2 Gustave Roussy Cancer Campus, Inserm U1030, Villejuif, France. 3 Gustave Roussy Cancer Campus, Biostatistics unit, Villejuif, France. 4 Gustave Roussy Cancer Campus, Pathology, Villejuif, France. 5 Gustave Roussy Cancer Campus, Surgery, Villejuif, France. 6 Institut Lumière-Matière, Université Lyon1-CNRS, UMR 5306, Villeurbanne, France. 7 NHTherAguIX, SA, Meylan, France. 8 Institut des Sciences Moléculaires d'Orsay, Université Paris Saclay, CNRS, Orsay, France. 9 Gustave Roussy Cancer Campus, Innovation Therapeutique et Essais Précoces, Villejuif, France. 10 Gustave Roussy Cancer Campus, Medical Oncology, Villejuif, France. 11 University of Kremlin Bicêtre, Faculty of Medicine, Le Kremlin-Bicêtre, France

Purpose/Objective:

This phase I trial aimed to assess the safety and determine the recommended Phase II dose (RP2D) of Gadolinium based AGuIX-nanoparticles (AGuIX-NP) in combination with chemoradiation and brachytherapy for patients with locally advanced cervical cancer.

Material/Methods:

Patients were treated with chemoradiation delivering 45 Gy in 25 fractions to the pelvis in combination with concurrent cisplatin 40mg/m² and followed with an image-guided adaptive brachytherapy according to standards of care. Patients received three injections of AGuIX-NP at two dose levels: 30 mg/kg and 50 mg/kg: two during external radiotherapy and one injection at time of brachytherapy. In addition to pharmacokinetic studies, the theranostic properties of AGuIX-NP were examined through serial MRI acquisitions and the MRI-based quantification capability of AGuIX-NP was assessed.

Results:

A total of 12 patients were treated with AGuIX-NP. No dose limiting toxicity (DLT) was observed in each dose level. Four patients experienced Serious Adverse Events (SAEs), two at level 1 (30 mg/kg) and two at level 2 (50 mg/kg). Among the four SAEs, only one occurred within the irradiated field: one patient treated at the level 2 (50 mg/kg) had transient cervical necrosis grade 2 occurring 6 months after end of brachytherapy. With median follow-up time of 27.4 months, all patients achieved first complete remission of the primary tumor. One patient had distant tumor recurrence. Progression-free survival rate at 24 months was 90% (95%CI: 59.6 – 98.2%). Fast disappearance in the blood was shown, followed with urinary elimination. Translational assays showed the possibility to perform non-invasive quantifications based on T1 mapping and a functional target volume could be delineated at time of brachytherapy, based on Gadolinium enhancement. The patient with grade 2 cervical necrosis had a 3 times higher NP uptake, compared to other patients treated at the same dose levels. Histological analyses showed a decrease in TIL population during and after treatment.