Glioblastoma is one of the central nervous system most aggressive and lethal cancers with poor overall survival rate. Systemic treatment of glioblastoma remains the most challenging aspect due to the low permeability of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), limiting therapeutics extravasation mainly in the core tumor as well as in its surrounding invading areas. It is now possible to overcome these barriers by using low-intensity focused ultrasound (LIFU) together with intravenously administered oscillating microbubbles (MBs). LIFU is a non-invasive technique using converging ultrasound waves which can alter the permeability of BBB/BTB to drug delivery in a specific brain/tumor region. This emerging technique has proven to be both safe and repeatable without causing injury to the brain parenchyma including neurons and other structures. Furthermore, LIFU is also approved by the FDA to treat essential tremors and Parkinson’s disease. It is currently under clinical trial in patients suffering from glioblastoma as a drug delivery strategy and liquid biopsy for glioblastoma biomarkers. The use of LIFU+MBs is a step-up in the world of drug delivery, where onco-therapeutics of different molecular sizes and weights can be delivered directly into the brain/tumor parenchyma. Initially, several potent drugs targeting glioblastoma were limited to cross the BBB/BTB; however, using LIFU+MBs, diverse therapeutics showed significantly higher uptake, improved tumor control, and overall survival among different species. Here, we highlight the therapeutic approach of LIFU+MBs mediated drug-delivery in the treatment of glioblastoma.

The deformable image registration (DIR) technique has the potential to realize the dose accumulation during radiotherapy. This study will analyze the feasibility of evaluating dose-volume parameters for the heart and left ventricular myocardium (LVM) by applying DIR. The electrocardiograph-gated four-dimensional CT (ECG-gated 4DCT) data of 21 patients were analyzed retrospectively. The heart and LVM were contoured on 20 phases of 4DCT (0%, 5%,…,95%). The heart and LVM in the minimum volume/dice similarity coefficient (DSC) phase (Volume _min/DSC _min) were deformed to the maximum volume/DSC phase (Volume _max/ DSC _max), which used the intensity-based free-form DIR algorithm of MIM software. The dose was deformed according to the deformation vector. The variations in volume, mean dose (D_mean), V₂₀, V₃₀ and V₄₀ for the heart and LVM before and after DIR were compared, and the reference phase was the Volume _max/DSC _max phase. For the heart, the difference between the pre- and post-registration Volume _min and Volume _max were reduced from 13.87 to 1.72%; the DSC was increased from 0.899 to 0.950 between the pre- and post-registration DSC _min phase relative to the DSC _max phase. The post-registration D_mean, V₂₀, V₃₀ and V₄₀ of the heart were statistically significant compared to those in the Volume _max/DSC _max phase (p < 0.05). For the LVM, the difference between the pre- and post-registration Volume _min and Volume _max were only reduced from 18.77 to 17.38%; the DSC reached only 0.733 in the post-registration DSC _min phase relative to the DSC _max phase. The pre- and post-registration volume, D_mean, V₂₀, V₃₀ and V₄₀ of the LVM were all statistically significant compared to those in the Volume _max/DSC _max phase (p < 0.05). There was no significant relationship between the variation in dose-volume parameters and the variation in the volume and morphology for the heart; however, the inconsistency of the variation in the volume and morphology for the LVM was a major factor that led to uncertainty in the dose-volume evaluation. In addition, the individualized local deformation registration technology should be applied in dose accumulation for the heart and LVM.

Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.

Introduction: Primary Central Nervous System Lymphoma (PCNSL) remains a diagnostic challenge due to the variable clinical manifestations. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly emerging as important and minimally invasive adjuncts to traditional biopsies. However, conventional pathology may be still essential to obtain a diagnosis. Patient concerns: A 56-year-old woman presented with a progressive headache, dizziness, blurred vision, and lower limbs weakness with dysesthesia. Atypical clinical and radiological presentations, previous empirical treatment in another hospital, together with the patient's refusal to stereotactic brain biopsy made it challenging to diagnose. Her status deteriorated continuously during hospitalization. Diagnosis: Lumber punctual was performed, and CSF cytological analysis revealed malignancy cells with a high nuclear-cytoplasmic ratio. However, these cells were too loose to perform immunohistochemical stains. Genetic aberrations detections with CSF and peripheral blood sample were also inconclusive. We made a “cell-block” using the sedimentary cells collected from CSF collected through multiple aspirations via an Omaya reservoir. We further performed cytopathological and immunohistochemical analysis using this “cell-block,” which finally confirmed the diagnosis of diffuse large-B cell PCNSL. Interventions: Intracranial chemotherapy began afterwards (MTX 15 mg and dexamethasone 5 mg, twice per weeks). Outcomes: Unfortunately, this patient was dead 2 weeks later due to severe myelosuppression and secondary septic shock. Conclusion: We provided “cell-block” method, which collects cell components from large amount of CSF for cytology and immunohistochemical analysis. “Cell-block” cytology can be an alternative diagnostic method in diagnosis of PCNSL.

Background: Cardiac activity could impact the accuracy of dose assessment for the heart, pericardium and left ventricular myocardium (LVM). The purpose of this study was to explore whether it is possible to perform dose assessment by contouring the cardiac structures on specific three-dimensional computed tomography (3DCT) images to reduce the impact of cardiac activity. Methods: Electrocardiograph-gated 4DCT (ECG-gated 4DCT) images of 22 patients in breath-hold were collected. MIM Maestro 6.8.2 (MIM) was used to reconstruct specific 3DCT images to obtain the Maximal intensity projection (MIP) image, Average intensity projection (AIP) image and Minimum intensity projection (Min-IP) image. The heart, pericardium and LVM were contoured in 20 phases of 4DCT images (0, 5%... 95%) and the MIP, AIP and Min-IP images. Then, a radiotherapy plan was designed at the 0% phase of the 4DCT images, and the dose was transplanted to all phases of 4DCT to acquire the dose on all phases, the accumulated dose of all phases was calculated using MIM. The dose on MIP, AIP and Min-IP images were also obtained by deformable registration of the dose. The mean dose (D_mean), V₅, V₁₀, V₂₀, V₃₀ and V₄₀ for the heart, pericardium and LVM in MIP, AIP and Min-IP images were compared with the corresponding parameters after dose accumulation. Results: The mean values of the difference between the D_mean in the MIP image and the D_mean after accumulation for the heart, pericardium and LVM were all less than 1.50 Gy, and the dose difference for the pericardium and LVM was not statistically significant (p > 0.05). For dose-volume parameters, there was no statistically significant difference between V₅, V₁₀, and V₂₀ of the heart and pericardium in MIP, AIP, and Min-IP images and those after accumulation (p > 0.05). For the LVM, only in the MIP image, the differences of V₅, V₁₀, V₂₀, V₃₀ and V₄₀ were not significant compared to those after dose accumulation (p > 0.05). Conclusions: There was a smallest difference for the dosimetry parameters of cardiac structures on MIP image compared to corresponding parameters after dose accumulation. Therefore, it is recommended to use the MIP image for the delineation and dose assessment of cardiac structures in clinical practice.