Predictive scoring systems for brain metastasis at diagnosis and at recurrence in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19020-e19020
Author(s):  
S. T. Maunglay ◽  
W. J. Fulp ◽  
A. Chiappori ◽  
G. R. Simon

e19020 Background: Brain metastasis (BM) is a major cause of mortality and morbidity in Non Small Cell Lung Cancer (NSCLC) but large studies analyzing potential factors that could be predictive of BM at diagnosis or recurrence are lacking. We have developed 2 predictive scoring models to identify the patients at risk. Methods: A retrospective analysis on 4,294 NSCLC cases, seen between 1994 and 2006, at the Moffitt Cancer Center and Research Institute, Tampa, FL was performed utilizing the cancer center's registry data. 477 (11.12%) patients had BM at the time diagnosis and additional 252 (5.82%) patients developed new BM as first recurrence. Results: For patients with BM at diagnosis, age younger than 63 years, non squamous histology and current or never smoking status were all significant in both univariate and multivariate analysis (N= 4174). Based on calculated odds ratios, a scoring system of 0 to 6 points was developed for these patients. Higher scores predicted higher risk for BM (0- 2=3.38%, 3- 4=9.93%, 5=13.65% and 6=21.03%; p <.0001). For patients with new BM at first recurrence, age younger than 63 years, non squamous histology, and the stage at diagnosis (i.e., BM risk in stage III>IV>II>I), were all significant in both univariate and multivariate analysis (N=4291). Based on calculated odds ratios, a scoring system of 0 to 7 points was developed for these patients. Higher scores predicted higher risk for BM (0–1=3.38%, 2–3=4.72%, 4–5= 8.76%, and 6–7=11.83%; p<.0001). Similar risk percentage results were seen after testing the 2 scoring systems in 3 chronologically divided patient groups. Conclusions: The 2 scoring systems developed based only on clinical data were predictive of BM in NSCLC at diagnosis and recurrence. These scoring systems should be helpful for establishing initial and follow up cranial imaging schedules in NSCLC patients. [Table: see text] No significant financial relationships to disclose.

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii15-iii16
Author(s):  
Raees Tonse ◽  
Muni Rubens ◽  
Haley Appel ◽  
Martin C Tom ◽  
Matthew D Hall ◽  
...  

Abstract Background Novel immunotherapeutic strategies, such as those targeting the PD-1/PD-L1 axis, are promising in patients with metastatic lung cancer and are often administered when tumors show PD-L1 positivity. The objective of this study was to analyze PD-L1 receptor discordance in tumor cell between the primary tumor and lung cancer brain metastasis (LCBM). Methods A systematic review of series published prior to April 2021 obtained from the Medline database of biopsied or resected LCBM evaluating PD-L1 discordance was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates. Results Six full-text articles (n=247 patients) with a median of 32 patients in each study (range: 24–73 patients) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases. The majority of patients (81%) were smokers, with 67% non-small cell lung cancer and 33% small cell lung cancer. The pooled estimate for overall PD-LI receptor concordance between primary and LCBM was 76% (95% CI: 52%-90). The positivity rate varied when analyzed by various cutoff levels of PD-L1 expression; for &lt;1% expression, it was 41% (95% CI: 22%-62%) for primary vs. 58% (95% CI: 35%-78%) for LCBM; for PD-L1 expression of 1–50%, it was 24% (95% CI: 13%-40%) vs. 19% (95% CI: 10%-33%); and for PD-L1 &gt;50% it was 12% (95% CI: 4%-33%) vs. 21% (95% CI: 14%-29%) (p=0.425). The pooled estimate for overall PD-LI receptor discordance between primary and LCBM was 17% (95% CI: 10%-27%). Meta-regression analysis showed that age, sex, smoking status, and histology were not associated with PD-LI receptor discordance. Conclusions PD-L1 status discordance in tumor cell occurs in approximately 20% of LCBM, with the greatest discordance in the &lt;1% expression category. Awareness of this discordance is important for the selection of immune checkpoint inhibitor therapy as well as in the analysis of patterns of failures.


2017 ◽  
Vol 18 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Ufuk Yilmaz ◽  
Esra Korkmaz Kirakli ◽  
Umit Gurlek ◽  
Yasemin Ozdogan ◽  
Bahri Gumus ◽  
...  

2019 ◽  
Vol 108 (3) ◽  
pp. 568-574
Author(s):  
Hidetoshi Yanai ◽  
Kai Kawashima ◽  
Kai Yazaki ◽  
Takeshi Numata ◽  
Kyoko Ota ◽  
...  

Aging ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 6734-6761 ◽  
Author(s):  
Chunhua Wei ◽  
Ruiguang Zhang ◽  
Qian Cai ◽  
Xican Gao ◽  
Fan Tong ◽  
...  

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.


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