Introduction Gestational trophoblastic diseases and neoplasias (GTDs and GTNs) comprise a spectrum of diseases arising from abnormally proliferating placental/trophoblastic tissue following an antecedent molar or non-molar pregnancy. These can spread to the brain hematogenously in about 10% of patients, mostly in high-risk disease. The optimal management of patients with brain metastases from GTN is unclear, with multiple systemic regimens under use and an uncertain role for radiotherapy.Areas covered Here, we review the epidemiology, workup, and treatment of GTN with central nervous system (CNS) involvement. Literature searches in PubMed and Google Scholar were conducted using combinations of keywords such as 'gestational trophoblastic disease,' 'gestational trophoblastic neoplasia,' 'choriocarcinoma,' and 'brain metastases.'Expert opinion Systemic therapy is the frontline treatment for GTN with brain metastases, and radiotherapy should only be considered in the context of a clinical trial or for resistant/recurrent disease. Surgery has a limited role in palliating symptoms or relieving intracranial pressure/bleeding. Given the highly specialized care these patients require, treatment at a high-volume referral center with multidisciplinary collaboration likely leads to better outcomes. Randomized trials should be conducted to determine the best systemic therapy option for GTN.
The most recent local study on the incidence of histological subtypes of all brain and spinal tumours treated surgically was published in 2000. In view of the outdated data, we investigated the presenting characteristics, histological subtypes and outcomes of adult patients who underwent surgery for brain or spinal tumours at our institution.A single-centre retrospective review of 501 patients who underwent surgery for brain or spinal tumours from 2016 to 2020 was conducted. The inclusion criteria were (a) patients who had a brain or spinal tumour that was histologically verified and (b) patients who were aged 18 years and above at the time of surgery.Four hundred and thirty-five patients (86.8%) had brain tumours and 66 patients (13.2%) had spinal tumours. Patients with brain tumours frequently presented with cranial nerve palsy, headache and weakness, while patients with spinal tumours frequently presented with weakness, numbness and back pain. Overall, the most common histological types of brain and spinal tumours were metastases, meningiomas and tumours of the sellar region. The most common complications after surgery were cerebrospinal fluid leak, diabetes insipidus and urinary tract infection. In addition, 15.2% of the brain tumours and 13.6% of the spinal tumours recurred, while 25.7% of patients with brain tumours and 18.2% of patients with spinal tumours died. High-grade gliomas and metastases had the poorest survival and highest recurrence rates.This study serves as a comprehensive update of the epidemiology of brain and spinal tumours and could help guide further studies on brain and spinal tumours.
As novel systemic therapies allow patients to live longer with cancer, the risk of developing central nervous system (CNS) metastases increases and providers will more frequently encounter emergent presentation of brain metastases (BM) and leptomeningeal metastases (LM). Management of these metastases requires appropriate work-up and well-coordinated multidisciplinary care. We set out to perform a review of emergent radiotherapy (RT) for CNS metastases, specifically focusing on BM and LM.We review the appropriate pathways for workup and initial management of BM and LM, while reviewing the literature supporting emergent treatment of these entities with surgery, systemic anti-cancer therapy, and RT. To inform this narrative review, literature searches in PubMed and Google Scholar were conducted, with preference given to articles employing modern RT techniques, when applicable. Due to the paucity of high-quality evidence for management of BM and LM in the emergent setting, discussion was supplemented by the authors' expert commentary.This work highlights the importance of surgical evaluation, particularly for patients presenting with significant mass effect, hemorrhagic metastases, or increased intracranial pressure. We review the rare situations where emergent initiation of systemic anti-cancer therapy is indicated. When defining the role of RT, we review factors guiding selection of appropriate modality, treatment volume, and dose-fractionation. Generally, 2D- or 3D-conformal treatment techniques prescribed as 30 Gy in 10 fractions or 20 Gy in 5 fractions, should be employed in the emergent setting.Patients with BM and LM present from a diverse array of clinical situations, requiring well-coordinated multidisciplinary management, and there is a paucity of high-quality evidence guiding such management decisions. This narrative review aims to more thoroughly prepare providers for the challenging situation of emergent management of BM and LM.
Reactive oxygen species (ROS) are a group of short-lived, highly reactive, oxygen-containing molecules that can induce DNA damage and affect the DNA damage response (DDR). There is unequivocal pre-clinical and clinical evidence that ROS influence the genotoxic stress caused by chemotherapeutics agents and ionizing radiation. Recent studies have provided mechanistic insight into how ROS can also influence the cellular response to DNA damage caused by genotoxic therapy, especially in the context of Double Strand Breaks (DSBs). This has led to the clinical evaluation of agents modulating ROS in combination with genotoxic therapy for cancer, with mixed success so far. These studies point to context dependent outcomes with ROS modulator combinations with Chemotherapy and radiotherapy, indicating a need for additional pre-clinical research in the field. In this review, we discuss the current knowledge on the effect of ROS in the DNA damage response, and its clinical relevance.
Glioblastoma (GBM) typically occurs as a primary tumour (i.e., primary GBM) and predominantly affects elderly patients. The remaining ~10% occur as a result of malignant progression from lower grade astrocytic tumours (i.e., secondary GBM). Although there are no certain causative environmental agents, prior radiation exposure may play a role. We report on a patient who had been treated six years prior for a vestibular schwannoma with high-dose conventional radiotherapy and subsequently developed a rapidly fatal glioblastoma at the same location. The diagnosis was confirmed by routine histopathology as well as more advanced techniques, such as whole genome copy number analysis.
Compared to post-operative whole brain radiotherapy, resection cavity radiosurgery reduces impact on neuro-cognitive function and improves quality-of-life. However, coverage of the operative tract, in addition to tumour bed, may lead to large treatment volumes and inter-observer variability. We hypothesized that pre-operative radiosurgery reduces target volume size and inter-observer variability compared to post-operative radiosurgery.We identified 10 consecutive patients, with solitary brain metastasis, treated with post-operative cavity radiosurgery.Pre- and post-operative axial T1 contrast MRI were co-registered with the planning CT scans. Three radiation oncologists independently contoured the target volumes on the pre- and post-operative imaging. A 2mm-PTV margin was utilized for both strategies and radiosurgery treatment plans were generated. The following parameters were evaluated in the 2 plans: Mean target volume (cc), 50% isodose volume (cc), Inter-observer variability (Jaccard Index JI) and Conformity Index (CI).There was no significant difference in the mean target volume, nor 50% isodose volume, between pre- and post-operative strategies. (17.6 (95% CI 9.98 - 25.22) versus 19.4 (95% CI 10.11 - 28.69) cc, P=0.80; 61.7 (95% CI 38.4 - 85.0) vs 77.7 (95% CI 34.94 - 120.46) cc, P=0.65). There was significantly less inter-observer variability and improved conformity in the pre-operative group (Mean JI 0.84(95% CI 0.82 - 0.86) versus 0.70 (95% CI 0.62 - 0.78), P = 0.005; Mean CI 1.32 (95% CI 1.26 - 1.38) vs 1.45 (95% CI 1.36 - 1.54), P= 0.01). Planned subgroup analysis did not reveal any significant difference (between pre- vs post-op) in the mean volume of cystic versus non-cystic metastasis. Deep lesions (>2.5cm from dura) had a larger post-operative target volume (25.8 (95% CI 15.1 - 36.5) vs 12.3 (95% CI 6.54 - 18.06) cc, P=0.06) compared to superficial lesions.Pre-operative radiosurgery has less inter-observer variability and improved plan conformity. However, there was no difference in mean target volume between the pre- versus post-operative radiation. Contouring guidelines, and peer review, may help to reduce inter-observer variability for cavity radiosurgery.
Spine tumors may arise within or surrounding the spinal cord and/or vertebral column. Spinal tumors can be benign or malignant. Based on their epicenter, they may be classified as intradural-intramedullary, intradural-extramedullary, or extradural. Of these, extradural lesions are the most common, and are typically metastatic. Primary bone tumors of the spinal column comprise 5% of all primary skeletal tumors. The majority of primary spinal column tumors are benign, with malignant tumors comprising only 20%. Overall, spine metastases are the most common malignant spine tumor, and these usually arise from primaries such as lung, breast, and prostate cancers. The advent of improved systemic therapies leading to improved survival and the frequent use of imaging has positioned metastatic spine disease as the new epidemic in oncology. For spine tumors, establishing the correct diagnosis is heavily reliant on magnetic resonance imaging and histological confirmation. In this review, we will provide an overview of the epidemiology, radiological and histopathological features, and the natural history of key primary (benign and malignant) spinal cord and column tumors and metastatic spine tumors. Treatment principles for primary spinal cord or column tumors are aimed toward curative resection, whereas palliative resection forms the treatment principle for most metastatic tumors.
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