Review - Late toxicity of abdominal and pelvic radiotherapy for childhood cancer

As survival improves in childhood cancer, prevention of late treatment-related toxicity in survivors becomes increasingly relevant. Radiotherapy is an important contributor to late toxicity. Therefore, minimizing radiation exposure to normal tissues is an important step towards improving the long-term therapeutic window of childhood cancer treatment. Since children are growing and developing, they are particularly vulnerable to radiation exposure. This makes the 'as low as reasonably achievable (ALARA)' principle even more important. In order to guide and achieve clinically meaningful dose reductions through advanced and emerging radiation techniques, it is important to investigate age-dependent relationships between radiation exposure to healthy tissues and late radiation-induced toxicity. In this review, we provide an overview of literature on the association between radiotherapy dose and late toxicity after abdominal and pelvic irradiation in childhood cancer. With this information, we aim to aid in decision-making regarding radiotherapy for childhood cancer. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 170 (2022) 27-36 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Study on intracranial meningioma using PET ligand investigation during follow-up over years (SIMPLIFY)

Purpose Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of C-11-methionine positron emission tomography (MET-PET) to the regular MRI follow-up. Methods This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and C-11-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's kappa. Results Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUVpeak T/N-cortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A kappa of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data. Conclusion In this pilot study, C-11-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging

Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma:a long-term follow-up study

Purpose: Response evaluation in patients with glioblastoma after chemoradiotherapy is challenging due to progressive, contrast-enhancing lesions on MRI that do not reflect true tumour progression. In this study, we prospectively evaluated the ability of the PET tracer 18F-fluorothymidine (FLT), a tracer reflecting proliferative activity, to discriminate between true progression and pseudoprogression in newly diagnosed glioblastoma patients treated with chemoradiotherapy. Methods: FLT PET and MRI scans were performed before and 4 weeks after chemoradiotherapy. MRI scans were also performed after three cycles of adjuvant temozolomide. Pseudoprogression was defined as progressive disease on MRI after chemoradiotherapy with stabilisation or reduction of contrast-enhanced lesions after three cycles of temozolomide, and was compared with the disease course during long-term follow-up. Changes in maximum standardized uptake value (SUVmax) and tumour-to-normal uptake ratios were calculated for FLT and are presented as the mean SUVmax for multiple lesions. Results: Between 2009 and 2012, 30 patients were included. Of 24 evaluable patients, 7 showed pseudoprogression and 7 had true progression as defined by MRI response. FLT PET parameters did not significantly differ between patients with true progression and pseudoprogression defined by MRI. The correlation between change in SUVmax and survival (p = 0.059) almost reached the standard level of statistical significance. Lower baseline FLT PET uptake was significantly correlated with improved survival (p = 0.022). Conclusion: Baseline FLT uptake appears to be predictive of overall survival. Furthermore, changes in SUVmax over time showed a tendency to be associated with improved survival. However, further studies are necessary to investigate the ability of FLT PET imaging to discriminate between true progression and pseudoprogression in patients with glioblastoma

Richtlijn 'Hersenmetastasen' (revisie)

Improved survival of cancer patients results in an increase in the incidence of brain metastases. In addition, asymptomatic brain metastases are more often detected as a consequence of active screening. In patients with cancer and new neurological symptoms, MRI of the brain is indicated to assess the presence and number of brain metastases. Decisions concerning treatment of brain metastases should take place within a multidisciplinary team. Treatment is in the first instance focused on improvement or preservation of neurological functioning. The main treatment options for patients with brain metastases are whole brain radiotherapy, stereotactic radiosurgery/radiotherapy, and neurosurgical resection. The choice of treatment depends on the number and the location of the brain metastases, the general and neurological condition of the patient, the extent of extracranial tumour activity, and the expected results of treatment. The revised guideline supports the policy of whole brain radiotherapy not being the standard treatment following stereotactic radiosurgery or radiotherapy. In the case of complete resection, confirmed using early postoperative MRI, whole brain radiotherapy does not add to survival benefit, while patients may suffer from radiation-induced toxicity

Practice guideline 'Brain metastases' (revision)

Improved survival of cancer patients results in an increase in the incidence of brain metastases. In addition, asymptomatic brain metastases are more often detected as a consequence of active screening. In patients with cancer and new neurological symptoms, MRI of the brain is indicated to assess the presence and number of brain metastases. Decisions concerning treatment of brain metastases should take place within a multidisciplinary team. Treatment is in the first instance focused on improvement or preservation of neurological functioning. The main treatment options for patients with brain metastases are whole brain radiotherapy, stereotactic radiosurgery/radiotherapy, and neurosurgical resection. The choice of treatment depends on the number and the location of the brain metastases, the general and neurological condition of the patient, the extent of extracranial tumour activity, and the expected results of treatment. The revised guideline supports the policy of whole brain radiotherapy not being the standard treatment following stereotactic radiosurgery or radiotherapy. In the case of complete resection, confirmed using early postoperative MRI, whole brain radiotherapy does not add to survival benefit, while patients may suffer from radiation-induced toxicity.</p

TGF-beta Antibody Uptake in Recurrent High-Grade Glioma Imaged with Zr-89-Fresolimumab PET

Transforming growth factor-beta (TGF-beta) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-beta, and tumor uptake can be visualized and quantified with Zr-89-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using Zr-89-fresolimumab PET and to assess treatment outcome in patients with recurrent high-grade glioma treated with fresolimumab. Methods: Patients with recurrent glioma were eligible. After intravenous administration of 37 MBq (5 mg) of Zr-89-fresolimumab, PET scans were acquired on day 2 or day 4 after tracer injection. Thereafter, patients were treated with 5 mg of fresolimumab per kilogram intravenously every 3 wk. Zr-89-fresolimumab tumor uptake was quantified as maximum standardized uptake value (SUVmax). MR imaging for response evaluation was performed after 3 infusions or as clinically indicated. Results: Twelve patients with recurrent high-grade glioma were included: 10 glioblastomas, 1 anaplastic oligodendroglioma, and 1 anaplastic astrocytoma. All patients underwent Zr-89-fresolimumab PET 4 d after injection. In 4 patients, an additional PET scan was obtained on day 2 after injection. SUVmax on day 4 in tumor lesions was 4.6 (range, 1.5-13.9) versus a median SUVmean of 0.3 (range, 0.2-0.5) in normal brain tissue. All patients showed clinical or radiologic progression after 1-3 infusions of fresolimumab. Median progression-free survival was 61 d (range, 25-80 d), and median overall survival was 106 d (range, 37-417 d). Conclusion: Zr-89-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit