Influence of Initial Stage at Diagnosis on Length of Time to Develop Brain Metastasis as Initial Disease Recurrence in Non–Small-Cell Lung Cancer

2009 ◽  
Vol 10 (5) ◽  
pp. E15
Author(s):  
Soe Maunglay ◽  
William Fulp ◽  
Alberto Chiappori ◽  
George Simon
2021 ◽  
Vol 14 (10) ◽  
pp. e244108
Author(s):  
Alex Fitzhugh ◽  
Alison Corr ◽  
Arshi Denton ◽  
Anthony Antoniou

A generally well 71-year-old man presented to his general practitioner with altered bowel habit and haematochezia. Colonoscopy revealed a malignant-appearing rectal mass, with histological features of extrapulmonary small cell carcinoma (EPSCC) of the rectum. Imaging demonstrated limited stage disease with a threatened circumferential resection margin. He was treated with a modified platinum chemoradiotherapy regimen for small cell lung cancer with an excellent response. Unfortunately, his cardiac function precluded surgery at the time and the patient subsequently developed hepatic metastases with local disease recurrence, and died 15 months following his initial diagnosis. Rectal EPSCC is a rare diagnosis, and this case represented a challenge for the multidisciplinary team given the limited evidence base. Medical therapy reflects extrapolation of small cell lung cancer treatment and the role of surgery is less clearly defined given aggressive and refractory disease is common. Immunotherapy, however, represents an exciting development for metastatic disease.


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 <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 >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 <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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