scholarly journals Preliminary application of 3.0T magnetic resonance chemical exchange saturation transfer imaging in brain metastasis of lung cancer

2019 ◽  
Author(s):  
Yonggui Yang ◽  
Xiaobo QU ◽  
Yihui HUANG ◽  
Gang GUO ◽  
Shaoyin DUAN

Abstract Background: Brain-metastasis of lung-cancer is very common and serious, and it is also one of the common causes of treatment failure. To investigate the clinical application of CEST technology in the diagnosis and prognosis evaluation of brain metastasis of lung cancer.Methods: 26 cases of lung cancer brain metastases, 15 cases of gliomas and 20 cases of normal controls were collected. MTR(3.5ppm) image obtained by GRE-EPI-CEST sequence using ASSET technique and APT software was observed. MTR-values(3.5ppm) were measured in the lesion-parenchymal, edema and non-focus areas, and the MTR image was compared with the conventional MRI. Statistical-Tests were ANOVA and t-test. Results:In the metastatic-tumor-group, the lesion-parenchymal, edema and non-focus areas were red-yellow, yellow-green, and green-blue, and the MTR-values were 3.29 ±1.14%,1.28 ±0.36%,1.26 ±0.31%. In glioma-group, the lesion-parenchymal, edema and non-focus areas were red, red-yellow, and the MTR-values of green-blue were 6.29 ±1.58%, 2.87 ±0.65%, 1.03 ±0.30%. The MTR-values of the corresponding areas in the normal-group were 1.07 ±0.22%,1.04 ±0.23%,1.06 ±0.24%. Traditional MR-images are in black-white contrast and no metabolic information is displayed. The MTR-values of three regions in metastatic-tumor-group and normal-group and glioma-group were significantly different, and the parenchymal area and edema area in metastatic-tumor-group were significantly different. There were significant differences in MTR-values between the non-lesion and edema areas, but there was no significant difference between the MTR-values in the edema area and the non-focus area. In glioma-group, there were significant differences in MTR-values between the parenchymal and edema areas and the non-focus areas, and the MTR-values between the edema and non-focus areas were significantly different.Conclusions: CEST can obtained the pseudo-color-images, which can reflect protein metabolism. In metastatic-tumor-group, the parenchymal area was red-yellow, green-blue, and the MTR-value was lower than that of glioma group, higher than that of normal-group. Observed the MTR-image color and MTR-value, the early diagnosis of brain metastases and the prognosis evaluation can be achieved on the molecular-imaging level. Trial registration: Grant No. 3502Z20144052.The experiments in the article did not involve the results of health care interventions for human participants.

2019 ◽  
Author(s):  
Yonggui Yang ◽  
Xiaobo QU ◽  
Yihui HUANG ◽  
Afsar Khan ◽  
Gen Yan ◽  
...  

Abstract Background: Lung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer(CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis. Methods: We included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis. Results: The lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29±1.14%,1.28±0.36%,and 1.26±0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29±1.58%, 2.87±0.65%, and 1.03±0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07±0.22%,1.04±0.23%, and 1.06±0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed. The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas. Conclusions: CEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging.


2020 ◽  
Author(s):  
Kejun Liu ◽  
Guanming Jiang ◽  
Ailing Zhang ◽  
Zhuanghua Li ◽  
Jun Jia

Abstract Background: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. Methods: We conducted a retrospective analysis of advanced NSCLC patients with brain metastases for EGFR targeted therapy from November 2013 to April 2018 at Dongguan People’s Hospital, Southern Medical University, China. A total of 43 patients were recruit in this study. Among them, 21 cases received icotinib (125 mg, thrice a day) and 22 cases received gefitinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was intracranial PFS (iPFS). The relationships between therapeutic arms and patients characteristics were performed using Pearson’s chi-square test or Fisher’s exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. Results: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P =0.62) and DCR (85.7% versus 81.8%, P =0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively (P =0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. Conclusions: Our study showed that icotinib and gefitinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.


2020 ◽  
Author(s):  
Kejun Liu ◽  
Guanming Jiang ◽  
Ailing Zhang ◽  
Zhuanghua Li ◽  
Jun Jia

Abstract Background: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. Methods: We conducted a retrospective analysis of advanced NSCLC patients with brain metastases for EGFR targeted therapy from November 2013 to April 2018 at Dongguan People’s Hospital, Southern Medical University, China. A total of 43 patients were recruit in this study. Among them, 21 cases received icotinib (125 mg, thrice a day) and 22 cases received gefitinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was intracranial PFS (iPFS). The relationships between therapeutic arms and patients characteristics were performed using Pearson’s chi-square test or Fisher’s exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. Results: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P =0.62) and DCR (85.7% versus 81.8%, P =0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively ( P =0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. Conclusions: Our study showed that icotinib and gefitinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18001-e18001
Author(s):  
Salah Eldeen Elmesidy ◽  
Mahmoud Abdelsalam ◽  
Husam Zawam

e18001 Background: Incidence of cerebral metastasis is increasing among lung cancer patients. Many factors have been reported associated with increase risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in lung cancer patients. Methods: We retrospectively analyzed histologically proven lung cancer patients radiologically diagnosed of having brain metastases who presented to Kasr Al-Eini Center for Oncology (NEMROCK) in the period from 2004 till 2010, with follow up period of 6 months at least. The following factors were analyzed: age, gender, PS, smoking history, tumor size & grade preceding development of brain metastasis. Results: Our study included 403 patients. 67 patients (16.6%) experienced brain metastasis during the course of their disease. 40 (10%) patients had brain metastasis among other sites of distant spread at first presentation which represent 88.9% of patients presented with metastatic disease. In a median follow-up of 17.1 months (6-77) the time to develop brain metastasis (TTBM) for the whole group was 5 months (range 2-22 months) (95% CI : 4.3-7.7). The most important factor affecting the TTBM was the use of chemotherapy before developing brain metastasis with a median TTBM of 5.9 months (95%CI : 3.2-6.8) among those who received chemotherapy compared to 2 months among the patients who didn't receive chemotherapy (P= <0.0001). The second factor was PS at time of initial diagnosis (P= 0.027). The median OS after brain metastasis was 6 months (95% CI : 4.26-7.74). On univariate analysis, PS and use of chemotherapy after developing brain metastases showed statistically significant difference affecting OS. Conclusions: We concluded that PS as well as use of chemotherapy are the 2 main factors associated with shorter time to develop brain metastasis. PS and use of chemotherapy after developing brain metastases showed longer OS after developing brain metastases. Keywords: NSCLC, Brain metastasis, Egypt


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ling-yun Ye ◽  
Li-xiang Sun ◽  
Xiu-hua Zhong ◽  
Xue-song Chen ◽  
Song Hu ◽  
...  

Abstract Background Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood–brain barrier (BBB) is frequently impaired, forming blood–tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. Methods Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. Conclusions Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi55-vi55
Author(s):  
Adam Lauko ◽  
Assad Ali ◽  
Soumya Sagar ◽  
Addison Barnett ◽  
Hong Li ◽  
...  

Abstract BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i15-i15
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Nebras Warsi ◽  
Jetan Badhiwala ◽  
Alireza Mansouri

Abstract BACKGROUND: Brain metastases (BM) are common in non-small cell lung cancer (NSCLC), with approximately 10% of patients presenting with BM at the time of diagnosis. The aim of this systematic review was to critically evaluate the evolution of management paradigms for BM from NSCLC. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, and CENTRAL for randomized controlled trials (RCTs) published until October 2018. Comparative RCTs based on ≥ 50 patients were selected. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 3188 abstracts, 14 RCTs (2494 patients) met inclusion criteria. Median sample size was 97 (range 59–538). Most trials were open-label, parallel, superiority trials. All included patients aged ≥18 with histologically proven NSCLC and ≥1 BM proven on CT/MRI. The majority of trials (11/14) excluded patients with non-favorable performance status (ECOG, KPS, or WHO scales), prior SRS or WBRT, and/or leptomeningeal metastases. Interventions assessed included WBRT (11/14), SRS (3/14), targeted therapies (e.g. EGFR inhibitors, 5/14), and various chemotherapeutic regimens (12/14). Most trials (12/13) reported no significant difference in OS between interventions. 4/10 trials reported a difference in PFS, two of which only included patients with EGFR-mutant NSCLC; these showed a significant increase in PFS in patients managed with EGFR inhibitors. The other two trials reported longer PFS with sodium glycididazole + WBRT vs. WBRT alone (p=0.038) and temozolomide + SRS vs. SRS alone (p=0.003). The incidence of adverse events was consistent across most treatment groups. CONCLUSIONS: Most trials showed no significant improvement in OS; however, improvement in PFS was seen in several trials, most notably in EGFR-positive patients treated with EGFR inhibitors. Given the long-standing merit of radiation-based therapies for BM management, these data support the need for an in-depth meta-analysis assessing the comparative efficacy of current management paradigms for specific patient populations.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18010-18010
Author(s):  
J. R. Gingerich ◽  
E. Lau ◽  
L. Xie ◽  
S. Navaratnam

18010 Background: Controversies still exist in the optimal management of patients with meta- static brain cancer. Lung cancer is the most common cause of metastatic brain cancer and the present study examines the treatment pattern and clinical outcome of this group of patients. Methods: Using the provincial cancer registry, all patients in Manitoba, Canada, with a history of lung cancer diagnosed with brain metastases during 2003 and 2004 were identified and a detailed chart review was carried out. Univariate and multivariate logistic analysis were used to identify significant variables affecting 1-year survival. Results: A total of 229 patients were identified of which 112 were male. The median age was 65 (range = 39–90). Of these patients, 69% had non-small cell lung cancer, 17% had small cell cancer, and 14% did not have the histological diagnosis available. A single brain metastasis, 2–4 brain metastases, and >4 brain metastases was identified in 25%, 25%, and 44% of the patients, respectively. The treatments for brain metastases were surgery (8%), gamma-knife radiosurgery (GKS) (7%), whole brain radiotherapy (WBRT) (62%), and no treatment (22%). Median survival for all patients was 98 days. On univariate analysis, 1-year survival was significantly influenced by surgery/GKS, age < 65, and controlled systemic disease (Odds ratio = 7.90; 5.43; 3.72 respectively, P < 0.02 for all) but not by sex, number of brain metastases or time from initial diagnosis to brain metastasis. On multivariate analysis, surgery/GKS and age remained significant (Odds ratio = 5.56, and 4.80, P < 0.01). Median survival (days) by treatment type were: surgery/GKS = 297(178–461), WBRT = 105(82–119), none = 39(29–50); log rank <0.001. Conclusions: In our patient population, with metastatic brain cancer arising from the lung, aggressive focal therapy (surgery or GKS) in younger patients (< 65) was associated with significantly better overall survival. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21740-e21740
Author(s):  
Salma Ait Batahar

e21740 Background: Lung cancer is the first cause of death by cancer worldwide. Brain metastases in lung cancer are associated to an even poorer prognosis of this cancer. Identifying patients with a higher risk of developing brain cancer may help their prognosis by including systematic brain radiotherapy to their treatment. But what are risk factors of brain metastasis occurrence in lung cancer patients? Methods: To answer this question, we conducted a case control study comparing two groups of lung cancer patients. The cases group included 35 lung cancer patients with brain metastasis at the moment of diagnosis while the control group was made of 49 lung cancer patient with no brain metastasis at the moment of diagnosis. Many parameters were compared between the two groups such as: professional exposure, type and duration of smoking, medical history, clinical and radiological presentation as well as the histological type of the carcinoma. Results: The mean age was 56 for the cases group and 61 for the control group. Nonsmokers represented 14% in the cases group and 4% in the control group. The average smoking was 34 pack-year for the cases group and 31 pack-year for the control group and in both groups 51% of patients smoked a mixture of tobacco and Cannabis. 36% of the control group patients had an exposure to a professional carcinogen while 48% of the cases group patients had one. Digital clubbing was found in 62% of cases group patients and in 51% of the control group patients. 17% of the cases group patients had two more metastases outside the lungs and other than the brain ones while this rate was only 6% for the control group patients. The mean level of LDH (Lactate Dehydrogenase) was 340 U/L for the cases group and 342 U/L for the control group while the CRP (C- reactive protein) one was 78 mg/L for the cases group and 59 mg/L for the control group. The main histological type found in both groups was Adenocarcinoma (25% in the cases group and 18% in the control group) followed by the poorly differentiated carcinoma in the cases group and the squamous cell carcinoma in the control group. Small cell carcinoma was found in 5% of the patients with brain metastases and in 8% of the patients without brain metastases. Conclusions: Patients with brain metastases have a higher professional carcinogens exposure, a higher percentage of nonsmokers, more digital clubbing, and higher CRP levels than patients with no brain metastases. They also have more than one metastasis at the moment of the diagnosis and the predominant histological types are Adenocarcinoma and poorly differentiated carcinoma.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19030-e19030
Author(s):  
M. Shenglin ◽  
X. Yaping ◽  
Y. Xinmin ◽  
Y. Yang

e19030 Background: The detection of brain metastasis(BM) is becoming increasingly common in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate clinical course, prognostic significance, and treatment efficacy in patients with brain metastasis. Methods: The records of all patients with BM from December 2003 to January 2007 were reviewed, and a retrospective study of 251 patients with cytologically and histologically diagnosed NSCLC and brain metastasis detected by cranial computed tomography or magnetic resonance imaging was performed. Variables analyzed included the recursive partitioning analysis (RPA) grouping, weight loss, LDH in blood serum, sex, age, time of brain metastasis (synchronous vs. metachronous), number of brain metastases, maximum diameter of largest brain lesion, Karnofsky performance status, histologic type (adenocarcinoma vs. other types of NSCLC), TNM stage (without consideration of brain involvement), and the treatment modality used for both the primary NSCLC tumor and brain metastasis. Results: The overall 1-, 2- and 3-year survival rates were 34.1%, 13.7% and 8.7% with a median survival time of 9.0 months (95% CI 8.04–9.97 months). On multivariate analysis, RPA grouping, weight loss, LDH in blood serum and treatment were independent prognostic factors. The median overall survival (OS) time of chemotherapy alone, whole brain radiotherapy (WBRT) alone, surgery alone, WBRT with chemotherapy, surgery with chemoradiation, WBRT with Gefitinib and others management was 6.0, 9.0, 12.0, 9.0, 22.0, 13.0 and 4.0 months, respectively, which were significantly different (X2=43.104, P=0.000). The stratify analysis indicated the median OS of patients received concurrent WBRT/chemotherapy (13.0 months) was longer than it of patients received sequential WBRT/chemotherapy (9.0 months) (X2=3.89,P=0.049). Conclusions: The main prognostic factors of BM from NSCLC of pretreatment are RAP grouping, weight loss and LDH in blood serum. The effect of combined treatment of surgery with chemoradiation is favorable and the choice of the patient is important. The survival are prolonged by active multidisciplinary management of brain metastases. [Table: see text]


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