11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.

Toxicity of external beam accelerated partial-breast irradiation (APBI) in adjuvant therapy of early-stage breast cancer: prospective randomized study.

BACKGROUND: Accelerated partial breast irradiation (APBI) is an alternative breast-conserving therapy approach where radiation is delivered in less time compared to whole breast irradiation (WBI), resulting in improved patient convenience, less toxicity, and cost savings. This prospective randomized study compares the external beam APBI with commonly used moderate hypofractionated WBI in terms of feasibility, safety, tolerance, and cosmetic effects. METHODS: Early breast cancer patients after partial mastectomy were equally randomized into two arms- external APBI and moderate hypofractionated WBI. External beam technique using available technical innovations commonly used in targeted hypofractionated radiotherapy to minimize irradiated volumes was used (cone beam computed tomography navigation to clips in the tumor bed, deep inspiration breath hold technique, volumetric modulated arc therapy dose application, using flattening filter free beams and the six degrees of freedom robotic treatment couch). Cosmetics results and toxicity were evaluated using questionnaires, CTCAE criteria, and photo documentation. RESULTS: The analysis of 84 patients with a median age of 64 years showed significantly fewer acute adverse events in the APBI arm regarding skin reactions, local and general symptoms during a median follow-up of 37 months (range 21-45 months). A significant difference in favor of the APBI arm in grade ≥ 2 late skin toxicity was observed (p = 0.026). Late toxicity in the breast area (deformation, edema, fibrosis, and pain), affecting the quality of life and cosmetic effect, occurred in 61% and 17% of patients in WBI and APBI arms, respectively. The cosmetic effect was more favorable in the APBI arm, especially 6 to 12 months after the radiotherapy. CONCLUSION: External APBI demonstrated better feasibility and less toxicity than the standard regimen in the adjuvant setting for treating early breast cancer patients. The presented study confirmed the level of evidence for establishing the external APBI in daily clinical practice. TRIAL REGISTRATION: NCT06007118.