SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. METHODS: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. DISCUSSION: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. TRIAL REGISTRATION: ClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Clinical applicability of and changes in perfusion MR imaging in brain metastases after stereotactic radiotherapy.

To assess the applicability of perfusion-weighted (PWI) magnetic resonance (MR) imaging in clinical practice, as well as to evaluate the changes in PWI in brain metastases before and after stereotactic radiotherapy (SRT), and to correlate these changes to tumor status on conventional MR imaging. Serial MR images at baseline and at least 3 and 6 months after SRT were retrospectively evaluated. Size of metastases and the relative cerebral blood volume (rCBV), assessed with subjective visual inspection in the contrast enhanced area, were evaluated at each time point. Tumor behavior of metastases was categorized into four groups based on predefined changes on MRI during follow-up, or on histologically confirmed diagnosis; progressive disease (PD), pseudoprogression (PsPD), non-progressive disease (non-PD) and progression unspecified (PU). Twenty-six patients with 42 metastases were included. Fifteen percent (26/168) of all PW images could not be evaluated due to localization near large vessels or the scalp, presence of hemorrhage artefacts, and in 31% (52/168) due to unmeasurable residual metastases. The most common pattern (52%, 13/25 metastases) showed a high rCBV at baseline and low rCBV during follow-up, occurring in metastases with non-PD (23%, 3/13), PsPD (38%, 5/13) and PU (38%, 5/13). Including only metastases with a definite outcome generally showed low rCBV in PsPD or non-PD, and high rCBV in PD. Although non-PD and PsPD may be distinguished from PD after SRT using the PW images, the large proportion of images that could not be assessed due to artefacts and size severely hampers value of PWI in predicting tumor response after SRT.

The ArcCHECK diode array for dosimetric verification of HybridArc.

The aim of this work is to evaluate dosimetric accuracy of a new treatment modality, HybridArc, in iPlan RT Dose 4.5 (BrainLAB, Feldkirchen, Germany) using a four-dimensional diode array (ArcCHECK, Sun Nuclear Corporation, Melbourne, USA). HybridArc is able to enhance dynamic conformal arcs with inversely planned elements. HybridArc plans for various sites (intracranial and extracranial) were constructed and after that these plans were recalculated for the ArcCHECK diode array with Monte Carlo (MC) and Pencil Beam (PB) dose algorithms in iPlan RT Dose. All measurements of these HybridArc plans were performed with 6 MV photon beams of a Novalis accelerator (BrainLAB, Feldkirchen, Germany) using the ArcCHECK device without and with an insert containing an ionization chamber. Comparison of the absolute dose distributions measured and calculated in iPlan RT Dose with the MC algorithm at the cylinder of the ArcCHECK diode array for HybridArc plans gives good agreement, even for the 2% dose difference and 2 mm distance-to-agreement criteria. The PB calculations significantly differ from the ArcCHECK measurements so that the MC algorithm is found to be superior to the PB algorithm in the calculation of the HybridArc plans. One of the drawbacks of the PB calculations in iPlan RT Dose is the too large arc step size of 10°. Use of a finer angular resolution may improve the PB results significantly.

Verification measurements and clinical evaluation of the iPlan RT Monte Carlo dose algorithm for 6 MV photon energy.

This study presents data for verification of the iPlan RT Monte Carlo (MC) dose algorithm (BrainLAB, Feldkirchen, Germany). MC calculations were compared with pencil beam (PB) calculations and verification measurements in phantoms with lung-equivalent material, air cavities or bone-equivalent material to mimic head and neck and thorax and in an Alderson anthropomorphic phantom. Dosimetric accuracy of MC for the micro-multileaf collimator (MLC) simulation was tested in a homogeneous phantom. All measurements were performed using an ionization chamber and Kodak EDR2 films with Novalis 6 MV photon beams. Dose distributions measured with film and calculated with MC in the homogeneous phantom are in excellent agreement for oval, C and squiggle-shaped fields and for a clinical IMRT plan. For a field with completely closed MLC, MC is much closer to the experimental result than the PB calculations. For fields larger than the dimensions of the inhomogeneities the MC calculations show excellent agreement (within 3%/1 mm) with the experimental data. MC calculations in the anthropomorphic phantom show good agreement with measurements for conformal beam plans and reasonable agreement for dynamic conformal arc and IMRT plans. For 6 head and neck and 15 lung patients a comparison of the MC plan with the PB plan was performed. Our results demonstrate that MC is able to accurately predict the dose in the presence of inhomogeneities typical for head and neck and thorax regions with reasonable calculation times (5-20 min). Lateral electron transport was well reproduced in MC calculations. We are planning to implement MC calculations for head and neck and lung cancer patients.

Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study.

OBJECTIVES: Most patients with advanced head and neck cancer receiving chemoradiotherapy need tube feeding for at least some weeks. For these periods gastrostomy tubes have advantages over nasogastric tubes. Tube feeding may start earlier and thus loss of weight may be limited if the gastrostomy tube already is in place. The objective of this study is to analyse the results of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement and early tube feeding. DESIGN: Retrospective chart review. SETTING: Multidisciplinary head and neck oncology team in a general hospital. PARTICIPANTS: Fifty consecutive patients with unresectable stage III and IV head and neck cancer treated with concurrent chemoradiotherapy. In all patients prophylactic PEG placement was performed. Tube feeding was initiated if food-intake became insufficient or loss of weight occurred. MAIN OUTCOME MEASURES: Loss of weight during treatment, complication rate, PEG duration. RESULTS: The mean loss of weight during treatment for all patients was only 2.8%. One complication of tube placement occurred: a colon perforation, treated successfully by surgery. The median duration of the PEG was 178 days. Three of the 17 patients (18%) with no evidence of disease (NED) still had a PEG at their last follow-up visit. Of the 26 patients who died of their cancer, 13 used the PEG until death. CONCLUSIONS: Loss of weight was limited after prophylactic gastrostomy placement and early tube feeding. Moreover, the complication rate was low. In 82% of the NED patients the PEG could eventually be removed.