scholarly journals Programmed Death Receptor Ligand One Expression May Independently Predict Survival In Non-Small Cell Lung Carcinoma Brain Metastases Patients Receiving Immunotherapy

2020 ◽  
Vol 108 (3) ◽  
pp. e715-e716
Author(s):  
A. Hulsbergen ◽  
M. Mammi ◽  
S. Nagtegaal ◽  
A. Lak ◽  
T. Smith ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Death Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Receptor Ligand ◽  
Cell Lung Carcinoma ◽  
Programmed Death ◽  
Death Receptor Ligand

scholarly journals 75. PROGRAMMED DEATH RECEPTOR LIGAND ONE EXPRESSION MAY INDEPENDENTLY PREDICT SURVIVAL IN NON-SMALL CELL LUNG CARCINOMA BRAIN METASTASES PATIENTS RECEIVING IMMUNOTHERAPY

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Alexander Hulsbergen ◽  
Marco Mammi ◽  
Steven Nagtegaal ◽  
Asad Malk ◽  
Vasileios Kavouridis ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
Death Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Receptor Ligand ◽  
Cell Lung Carcinoma ◽  
Programmed Death ◽  
Death Receptor Ligand

Abstract BACKGROUND Programmed death receptor ligand one (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. METHODS In this multi-institutional retrospective cohort study, we identified NSCLC-BM patients treated with PD-1/PD-L1 inhibitors after local BM treatment (radiotherapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess predictive value PD-L1 expression for overall survival (OS) and intracranial progression free survival (IC-PFS). RESULTS Forty-eight BM patients with available PD-L1 expression were identified. PD-L1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (HR = 0.44; 95% CI 0.19 – 1.02; p = 0.055). This effect persisted after correcting for lung-graded prognostic assessment (lung-GPA) and other identified potential confounders (HR = 0.24; 95% CI = 0.10 – 0.61; p = 0.002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR = 0.86 per 10% expression, 95% CI 0.77 – 0.98, p = 0.02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR = 0.54, 95% CI 0.26 – 1.14, p = 0.11). CONCLUSIONS In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-GPA. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.

scholarly journals Correlation Between Programmed Death Receptor-1 Expression in Tumor-Infiltrating Lymphocytes and Programmed Death Ligand-1 Expression in Non–Small Cell Lung Carcinoma

2018 ◽  
Vol 142 (11) ◽  
pp. 1388-1393 ◽  
Author(s):  
Paloma del C. Monroig-Bosque ◽  
Brandon Driver ◽  
Joel A. Morales-Rosado ◽  
Michael Deavers ◽  
David Tacha ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Death Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Disease ◽  
Cell Lung Carcinoma ◽  
Programmed Death ◽  
Infiltrating Lymphocytes

Context.— The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non–small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease. Objective.— To investigate the correlation of PD-1 and PD-L1 in non–small cell lung carcinoma tumor samples, with emphasis on stage I disease. Design.— Whole tissue sections from non–small cell lung carcinoma tumors were retrospectively evaluated by immunohistochemistry for PD-1 and PD-L1 expression. The scoring was based on the percentage of cells positive for PD-1 in TILs and PD-L1 in TCs and tumor-infiltrating immune cells (ICs). Results.— Expression of PD-1 in TILs was observed in 147 of 161 non–small cell lung carcinoma cases (91%). The majority of cases negative for PD-1 also lacked PD-L1 in TCs. The 68 cases with highest PD-1 expression in TILs included 33 (49%) with expression of PD-L1 in TCs and ICs. Strong correlations were observed in patients with elevated PD-1 expression in TILs and PD-L1 in TCs (P = .01) and ICs (P = .003). Expression of PD-1 also correlated with increased PD-L1 in TCs and ICs when the 2 were grouped together (P < .001). Finally, stage I patients with negative PD-1 and PD-L1 expression showed trends toward increased disease-specific survival. Conclusions.— Expression of PD-1 in TILs correlates with PD-L1 expression in both TCs and ICs. Furthermore, negative expression of PD-1 and PD-L1 suggest trends toward disease-specific survival, even in early disease stages.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object.Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival.Methods.A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival.The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging.Conclusions.Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

Risk factors affecting survival after brain metastases from non—small cell lung carcinoma: a follow-up study of 70 patients

2001 ◽  
Vol 95 (4) ◽  
pp. 595-600 ◽  
Author(s):  
John M. Abrahams ◽  
Maria Torchia ◽  
Mary Putt ◽  
Larry R. Kaiser ◽  
Kevin D. Judy
Keyword(s):  
Brain Metastases ◽  
Survival Time ◽  
Lung Carcinoma ◽  
Median Survival Time ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
Fine Print

Object. The authors present their experience with the treatment of brain metastases from non—small cell lung carcinoma (NSCLC). Methods. A retrospective review was conducted in which records from 74 patients treated at the authors' institution between 1994 and 1999 were assessed. Survival and functional outcome were reviewed relative to individual patient variables. The median survival time was 12.9 months, with 1-, 2-, and 5-year survival milestones reached by 52.2%, 30.7%, and 18.1% of patients, respectively. Patients were stratified into groups composed of those with synchronous brain metastases (tumors diagnosed within 3 months of NSCLC) and metachronous brain metastases (tumors diagnosed 3 months after NSCLC). The median survival time and 5-year survival rate were 18 months and 28.9% for metachronous, compared with 9.9 months and 0% for synchronous brain metastases. In univariate analyses, the stage of brain metastases, an initial Karnofsky Performance Scale (KPS) score of 90 or less, and conservative therapy for NSCLC were associated with worse outcomes (p < 0.05). In analyses in which tumors were stratified by synchronous compared with metachronous brain metastases, a preoperative KPS score of 90 or less and radiation therapy (RT) alone for brain metastases were associated with worse outcomes in patients with metachronous brain metastases but not with synchronous tumors (p < 0.05). When stratified by preoperative KPS score, the synchronous brain metastases stage or treatment of brain metastases with RT alone were associated with worse outcome in patients with KPS scores of 100, but had no discernible effect on patients with KPS scores of 90 or less (p < 0.05). Conclusions. The tumor stage and preoperative KPS score were significantly associated with survival. Craniotomy plus RT significantly improved the prognosis in patients with metachronous brain metastases or those with a preoperative KPS score of 100.

Factors Affecting the Risk of Brain Metastases After Definitive Chemoradiation for Locally Advanced Non–Small-Cell Lung Carcinoma

2001 ◽  
Vol 19 (5) ◽  
pp. 1344-1349 ◽  
Author(s):  
Theodore J. Robnett ◽  
Mitchell Machtay ◽  
James P. Stevenson ◽  
Kenneth M. Algazy ◽  
Stephen M. Hahn
Keyword(s):  
Brain Metastases ◽  
Brain Imaging ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Ii ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

PURPOSE: As therapy for locally advanced non–small-cell lung carcinoma (NSCLC) improves, brain metastases (BM) may become a greater problem. We analyzed our chemoradiation experience for patients at highest risk for the brain as the first failure site. METHODS: Records for 150 consecutive patients with stage II/III NSCLC treated definitively with chemoradiation from June 1992 to June 1998 at the University of Pennsylvania were reviewed. Most patients (89%) received cisplatin, paclitaxel, or both. All had negative brain imaging before treatment. Posttreatment brain imaging was performed for suspicious symptoms. Incidence of BM was examined as a function of age, sex, histology, stage, performance status, weight loss, tumor location, surgery, radiation dose, initial radiation field, chemotherapy regimen, and chemotherapy timing. RESULTS: Crude and 2-year actuarial rates of BM were 19% and 30%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (P < .04) versus stage II/IIIA. Histology alone was not significant (P < .12), although patients with IIIB nonsquamous tumors had an exceptionally high 2-year BM rate of 42% (P < .01 v all others). Examining treatment-related parameters, crude and 2-year actuarial risk of BM were 27% and 39%, respectively, in patients receiving chemotherapy before radiotherapy and 15% and 20%, respectively, when radiotherapy was not delayed (P < .05). On multivariate analysis, timing of chemotherapy (P < .01) and stage IIIA versus IIIB (P < .01) remained significant. CONCLUSION: Patients with later stage, nonsquamous NSCLC, particularly those receiving induction chemotherapy, have sufficiently common BM rates to justify future trials including prophylactic cranial irradiation.

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