Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non–Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection

Wasilewski, David; Radke, Josefine; Xu, Rihao; Raspe, Matthias; Trelinska-Finger, Anna; Rosenstock, Tizian; Poeser, Paul; Schumann, Elisa; Lindner, Judith; Heppner, Frank L.; Kaul, David; Suttorp, N; Vajkoczy, Peter; Frost, Nikolaj; Onken, Julia

doi:10.1001/jamanetworkopen.2022.9553

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…In recent years, related immunological studies have found that immune cell infiltration plays a key role in the tumor microenvironment in the formation, occurrence and development (31,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). The most concerned are the immune checkpoint protein PD-1 and its ligands PD-L1 and PDCD1LG2, tumor transforming growth factor B1 (TGFB1) and its receptors TGFB1R (48)(49)(50)(51)(52)(53)(54). TGFB1 plays an immunosuppressive role in the process of tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Zhou

Zhang

et al. 2022

Front. Med.

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Recent studies have found that the protein encoded by the FDX1 gene is involved in mediating Cuproptosis as a regulator of protein lipoylation and related to immune response process of tumors. However, the specific biological function of FDX1 in glioma is currently unclear. To explore the potential function of FDX1, this study explored the correlation between the expression of FDX1 in cancers and survival prognosis by analyzing the public databases of GEPIA and Cbioportal. Immune infiltration was analyzed by the TIMER2.0 database in tumors. The possible biological processes and functions of FDX1-related in glioma were annotated through gene enrichment. Relationship between Cuproptosis and autophagy was explored through gene co-expression studies. Summary and conclusions of this study: (1) FDX1 is highly expressed in gliomas and associated with poor prognosis in low-grade gliomas (LGG). (2) Gene annotation indicates that FDX1 is mainly involved in the tumor protein lipoylation and cell death. (3) FDX1 expression is positively correlated with the infiltration of immune cells. (4) LIPT2 and NNAT, two other genes involved in lipoylation, may be unidentified marker gene for Cuproptosis. And the Cuproptosis genes related to FDX1 were positively correlated with the expression of autophagy marker genes Atg5, Atg12, and BECN-1. This evidence suggests that there may be some interaction between FDX1 mediated Cuproptosis and autophagy. In summary, FDX1 may serve as a potential immunotherapy target and prognostic marker for Glioma.

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Section: Introductionmentioning

confidence: 99%

Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Zhou

Zhang

et al. 2022

Front. Med.

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“…Brain metastases of peripheral tumors have been regarded as a terminal disease stage with a very poor prognosis and few therapeutic options [ 5 , 6 ]. Lung cancer is the most common tumor that metastasizes to the brain [29] .…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the brain has a predisposition for colonization by disseminated lung cancer cells, with up to 50% of lung cancer patients developing brain metastases [ 4 , 5 ]. Historically, the brain has been regarded as a shelter for lung cancer cells due to its unique anatomical structures, immune environment, and metabolic constraints; therefore, brain metastases have been considered a terminal disease stage with a poor prognosis and a median overall survival period of approximately 3–8 months [ 6 , 7 ]. Although promising advances have been made to decipher the mechanism of brain metastases, the prognosis of lung cancer patients with brain metastasis remains poor [8] , [9] , [10] .…”

Section: Introductionmentioning

confidence: 99%

Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment

Chen

et al. 2023

Translational Oncology

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“…Data censoring was 1 st of December 2022. Patient data were identified as previously described using an institutional database (SAP, Walldorf, Germany) as well as the Charité Comprehensive Cancer Center (CCCC) Registry 16 . Patients with a histopathological confirmation of an intracerebral manifestation of non-small cell lung cancer (NSCLC), breast cancer, melanoma, renal cell carcinoma (RCC), colorectal cancer (CRC), esophageal cancer or gastric cancer or unknown primary tumor were included.…”

Section: Methodsmentioning

confidence: 99%

Impact of Perioperative Dexamethasone in the Context of Neurosurgical Brain Metastasis Resection

Wasilewski

Bukatz

Peukert

et al. 2023

Preprint

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Background: Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate whether perioperative dexamethasone in brain metastases is linked to survival. Methods: Retrospective data on perioperative dexamethasone dosage in resected brain metastasis patients at three hospital sites of the Charite from 2010-2022 were collected. Cut-off values for cumulative perioperative dexamethasone dose as a continuous predictor variable for survival were determined using maximally selected rank statistics. Patients were dichotomized based on determined cut-offs of cumulative dexamethasone (pre-operative: < 40 mg vs ≥ 40 mg; post-operative: < 180 mg vs ≥ 180 mg) and pre- and postoperative: < 281 mg vs ≥ 281 mg). Medical records included baseline demographic, radiological, histopathological and treatment-related characteristics. Based on cut-off values for dexamethasone downstream statistical analyses included Kaplan-Meier, Cox proportional hazards regression for overall survival with adjustment for potential confounders including age, gender, Karnofsky performance status and presence of extracranial metastasis via propensity score matching. Results: 539 patients were included. Median follow-up time was 58,97 months. After adjusting for age, gender, Karnofsky performance status and presence of extracranial metastasis patients with higher cumulative perioperative dexamethasone (≥281 mg) showed shorter survival (HR: 1.47 (1.20-1.80, p<0.001) as compared to patients with lower cumulative doses (<281 mg). This effect remained significant after correction for patients that died within 2 months after resection and for patients with KPS below 50% and, independently from this approach performing propensity score matched-based analysis of the total cohort of patients, respectively. Conclusion: Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases.

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Effectiveness of Immune Checkpoint Inhibition vs Chemotherapy in Combination With Radiation Therapy Among Patients With Non–Small Cell Lung Cancer and Brain Metastasis Undergoing Neurosurgical Resection

Cited by 11 publications

References 35 publications

Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment

Impact of Perioperative Dexamethasone in the Context of Neurosurgical Brain Metastasis Resection

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