Sodium Fluorescein-Guided Surgery for Resection of Brain Metastases from Lung Cancer: A Consecutive Case Series Study and Literature Review.

(1) Introduction and objective: Surgical resection plays an important role in the multidisciplinary treatment of lung cancer patients with brain metastases (BMs). Precisely distinguishing the tumor border intraoperatively to improve and maximize the extent of resection (EOR) without causing permanent neurological defects is crucial but still challenging. Therefore, we introduced our experience of utilizing sodium fluorescein (SF) in microneurosurgery of BMs from lung cancer. This study aims to evaluate whether the use of SF-guided surgery has a positive impact on postoperative outcomes. (2) Materials and methods: A retrospective study was performed to collect data on a consecutive case series of patients with BMs from lung cancer who underwent surgical resection from January 2020 to December 2021 at the Department of Neuro-Oncology, Chongqing University Cancer Hospital. A total of 52 patients were enrolled, of which 23 received SF-guided surgery and 29 did not. EOR was assessed pre- and postoperatively on T1 contrast-enhanced MRI. Clinical and epidemiological data as well as follow-up were gathered and analyzed. (3) Results: Compared with the non-SF-guided group, the SF-guided group revealed a significantly better EOR (87.0% vs. 62.1%) and a lower incidence of local recurrence (8.7% vs. 34.5%). Survival benefits were seen in patients with NSCLC, patients who were undergoing SF-guided surgery, and patients receiving postoperative systemic therapy. (4) Conclusions: SF-guiding under the YELLOW 560 nm filter is a safe and feasible tool for improving the EOR in patients with BMs from lung cancer, leading to better local recurrence control and prolonged survival.

Computational Modeling of Interstitial Fluid Pressure and Velocity in Non-small Cell Lung Cancer Brain Metastases Treated With Stereotactic Radiosurgery.

Background: Early imaging-based treatment response assessment of brain metastases following stereotactic radiosurgery (SRS) remains challenging. The aim of this study is to determine whether early (within 12 weeks) intratumoral changes in interstitial fluid pressure (IFP) and velocity (IFV) estimated from computational fluid modeling (CFM) using dynamic contrast-enhanced (DCE) MRI can predict long-term outcomes of lung cancer brain metastases (LCBMs) treated with SRS. Methods: Pre- and post-treatment T1-weighted DCE-MRI data were obtained in 41 patients treated with SRS for intact LCBMs. The imaging response was assessed using RANO-BM criteria. For each lesion, extravasation of contrast agent measured from Extended Tofts pharmacokinetic Model (volume transfer constant, Ktrans) was incorporated into a computational fluid model to estimate tumor IFP and IFV. Estimates of mean IFP and IFV and heterogeneity (skewness and kurtosis) were calculated for each lesion from pre- and post-SRS imaging. The Wilcoxon rank-sum test was utilized to assess for significant differences in IFP, IFV, and IFP/IFV change (Δ) between response groups. Results: Fifty-three lesions from 41 patients were included. Median follow-up time after SRS was 11 months. The objective response (OR) rate (partial or complete response) was 79%, with 21% demonstrating stable disease (SD) or progressive disease (PD). There were significant response group differences for multiple posttreatment and Δ CFM parameters: post-SRS IFP skewness (mean -0.405 vs. -0.691, p = 0.022), IFP kurtosis (mean 2.88 vs. 3.51, p = 0.024), and IFV mean (5.75e-09 vs. 4.19e-09 m/s, p = 0.027); and Δ IFP kurtosis (mean -2.26 vs. -0.0156, p = 0.017) and IFV mean (1.91e-09 vs. 2.38e-10 m/s, p = 0.013). Posttreatment and Δ thresholds predicted non-OR with high sensitivity (sens): post-SRS IFP skewness (-0.432, sens 84%), kurtosis (2.89, sens 84%), and IFV mean (4.93e-09 m/s, sens 79%); and Δ IFP kurtosis (-0.469, sens 74%) and IFV mean (9.90e-10 m/s, sens 74%). Conclusions: Objective response was associated with lower post-treatment tumor heterogeneity, as represented by reductions in IFP skewness and kurtosis. These results suggest that early post-treatment assessment of IFP and IFV can be used to predict long-term response of lung cancer brain metastases to SRS, allowing a timelier treatment modification.

Research progress on relationship between brain metastasis from lung cancer and ex-tracellular vesicles / 中国肿瘤临床

Extracellular vesicles (EVs) are vesicles like body of phospholipid bilayer membrane, which are able to mediate the transfer of genetic material. There are receptors, proteins and nucleic acids in the body, with carrying tumor genetic material, regulating tumor microenvironment, promoting tumor angiogenesis and mediating tumor cell metastasis. At present, it is found that there is a close re-lationship between the secretion and the metastasis of lung cancer. The main aspects of the brain metastasis of the lung cancer medi-ated by the exocrine body include the regulation of the microenvironment of the brain, the destruction of the blood-brain barrier, and the regulation of tumor cell pathology. The study on the relationship between the tumor and the metastasis of lung cancer may pro-vide more molecular targets for the development, diagnosis and treatment of lung cancer.

Comparison between Dual Arc VMAT and 7F-IMRT in the protection of hippocampus for patients during whole brain radiotherapy.

PURPOSE: The purpose of this study was to compare the dosimetric characteristics for protection of the hippocampus between dual arc VMAT (volumetric modulated arc therapy) and 7 fields intensity-modulated radiation therapy (7F-IMRT) for patients with brain metastases from lung cancer under the whole brain radiotherapy. METHODS: Based on ten cases with brain metastases from lung cancer, two types of radiotherapy plans were designed, namely, dual arc VMAT and 7F-IMRT. Provided that the clinical requirements were satisfied, the comparisons of target dose distribution, conformity index (CI), homogeneity index (HI), dose of organs at risk (OARs), monitor units (MU) and treatment time between dual arc VMAT and 7F-IMRT were investigated for their dosimetric difference. RESULTS: Both treatment plans met the requirements of clinical treatments. However, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT (P < 0.05). As to OARs, the mean maximum doses (Dmax) of hippocampus, eyes and optic nerves in the dual arc VMAT plan were all lower than those in 7F-IMRT plan (P < 0.05), but the result had no statistical significance (P < 0.05) for the maximum dose of lens. Compared with 7F-IMRT, dual arc VMAT reduced the average number of MU by 67% and the average treatment time by 74%. Therefore, treatment time was shortened by dual arc VMAT. CONCLUSION: With regards to the patients with brain metastases from lung cancer under the whole brain radiotherapy, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT under the precise of meeting the clinical requirements. In addition, dual arc VMAT remarkably reduced the irradiation dose to OARs (hippocampus, eyes and optic nerves), MU and treatment time, as well, guaranteed patients with better protection.

Comparison between the establishment methods of mouse models of lung cancer brain metastases by intrathoracic orthotopic implantation and by left ventricular injection / 中国实验动物学报

Objective To establish an appropriate animal model of brain metastases from lung cancer in nude mice by thoracic orthotopic implantation in the chest or left ventricular injection , and to serve further studies on the mechanisms of lung cancer brain metastasis .Methods PC-9 cells (1 ×106/0.1 mL) in logarithmic phase were respectively injected into 18 nude mice by orthotopic implantation in the chest or left ventricular injection ( n=9 each group ) .The statuses of nude mice were observed after implantation .Animals showing clear signs of dyscrasia were killed .At autopsy, the lung, brain, liver and kidney were removed and histological sections were stained with H /E to detect the presence of tumor cells . Results In the thoracic orthotopic implantation group , three weeks after implantation , the number 4, 6, 9 mice showed tumor nodules in the chest wall , they began to lose weight in the fourth to sixth week differently , showing signs of dyscrasia gradually , and were sacrificed at the fifth to seventh week .The thoracotomy revealed that the whole thorax was occupied by many large lung cancer masses , spreading into bilateral ribs , pleura and spinal vertebra , with scarce eroded , compressed , pale and distorted lung tissues left .Histological examination with HE staining showed the presence of neoplasms in their lung tissues but only the number 6 mouse showed metastatic lesions in the brain tissue .In the left ventricular injection group, the mice almost began to lose weight in the third week simultaneously and became moribund slowly , which were all sacrificed at the fourth week .After thoracotomy , the thoraxes were clear except the number 11 and 18 mice which appeared 2-3 tiny tumor foci in the chest wall , with normal lung tissues .Histological examination with HE staining showed the pres-ence of brain metastases in all the nine mice .The rate of brain metastases from lung cancer in the left ventricular injection group was 100%, compared with 11.1% in the thoracic orthotopic implantation group .Conclusions The establishment method of mouse model by left ventricular injection shows significantly higher rate of lung cancer brain metastases than that by thoracic orthotopic implantation .

Effect of radiotherapy combined with elemene injection on lung cancer treatment / 中国生化药物杂志

Objective To study the clinical effects on patients with brain metastases from lung cancer combined with Elemene Injection and radiotherapy. Method 86 patients with brain metastases from lung cancer were randomly divided into control group and treatment group, 43 cases in each group. Control group was given conventional radiotherapy treatment, while treatment group combined Elemene Injection with radiotherapy. Results Compared with control group, treatment group’s disease control effect was obviously better. Survival rates after treatment for six months, one year, three years were higher than control group, and the number of adverse reactions were lower. Serum MMP-2 and MMP-9 levels were significantly greater. Radiotherapy plan time and total time in hospital for treatment were significantly shorter. Conclusion The combination of Elemene Injection with radiotherapy treatment for patients with brain metastases from lung cancer is very obvious.