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1.
Lung Cancer ; 153: 81-89, 2021 03.
Article in English | MEDLINE | ID: mdl-33465698

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors (ICI), such as anti-PD-1 agents, have become part of the standard of care treatment of advanced non-small cell lung cancer (NSCLC). Predictive biomarkers are needed to identify patients that benefit from anti-PD-1 treatments. Tumor infiltrating lymphocytes (TILs) and PD-L1 are major players in the ICI mechanism of action. In this study, we assess the impact of real-world clinicopathological variables, including TILs and PD-L1, on anti-PD-1 efficacy. METHODS: We performed a monocenter retrospective study in advanced NSCLC treated with nivolumab or pembrolizumab between January 2015 and February 2019. The impact of baseline clinical and pathological variables was assessed by univariate and multivariate models. TILs, defined as CD8+T-cells, and PD-L1 were scored in tumor and stroma, and correlated with progression free survival (PFS) and overall survival (OS). RESULTS: We included 366 patients of whom 141 were assessed for tumor and stromal TILs. The median follow-up time was 487 days. In the whole cohort, PFS was associated with high tumor PD-L1, high albumin and good performance. OS was associated with low LDH, high albumin, good performance and 'first-line treatment'. In the TILs subcohort, stromal TILs had the strongest impact on PFS and OS. Stromal TILs were a stronger marker for PFS and OS than tumoral TILs, tumoral PD-L1 or stromal PD-L1. Remaining factors for PFS and OS were albumin and albumin with LDH, respectively. CONCLUSIONS: This real-world study on clinicopathological features shows that stromal CD8 + TILs were the strongest predictor for PFS and OS in patients with advanced NSCLC on anti-PD-1 therapy. Other predictors for PFS and OS included albumin and albumin together with LDH, respectively. This study highlights the pivotal role of the stromal compartment in the mechanisms of action of ICI, and the need for further studies aiming to overcome this stromal firewall.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , B7-H1 Antigen , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Lymphocytes, Tumor-Infiltrating , Prognosis , Retrospective Studies
2.
Ann Oncol ; 22(1): 132-138, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20595452

ABSTRACT

BACKGROUND: published trials of concurrent chemoradiotherapy (CCRT) in stage III non-small-cell lung cancer (NSCLC) generally excluded patients with significant comorbidity. We evaluated outcomes in patients who were selected by using radiation planning parameters and were considered, despite comorbidity, fit enough to receive cisplatin-based chemotherapy. PATIENTS AND METHODS: from 2003 to 2008, 89 patients with stage III NSCLC fit to receive cisplatin-based chemotherapy and a V(20) <42% underwent CCRT at one center outside clinical trials. Most received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrent with involved-field thoracic radiotherapy between 46 and 66 Gy. RESULTS: median age was 64 years; performance status (PS) of zero, one or two in 20/64/5 patients; one or more comorbidities in 41.6%; 14% were treated previously for NSCLC. Median V(20) was 26.6% (range 4%-39.4%). Grade III esophagitis and pneumonitis occurred in 28.1% and 7.9% of patients, respectively, while 4.5% died during treatment. Median overall survival was 18.2 months [95% confidence interval (CI) 13.1-23.3 months]. Independent prognostic factors for overall survival were PS (0 versus ≥ 1, P = 0.041) and planning target volume (P = 0.022). CONCLUSIONS: patients with significant comorbidity who are fit to undergo cisplatin-based CCRT achieve median survivals similar to that reported in phase III trials and with relatively few late toxic effects.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Combined Modality Therapy , Comorbidity , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasm Staging , Survival Rate , Treatment Outcome , Gemcitabine
3.
Ned Tijdschr Geneeskd ; 141(3): 152-4, 1997 Jan 18.
Article in Dutch | MEDLINE | ID: mdl-9053763

ABSTRACT

Two male patients aged 47 and 26 ears had long-standing, slowly progressive complaints of sudden headache, nausea, vomiting and faintness. Their symptoms grew much worse during an active holiday in the tropics. Phaeochromocytoma was diagnosed. After resection the complaints resolved. A slumbering phaeochromocytoma may become manifest due to increased vasodilation and exertion during a temporary stay in the tropics.


Subject(s)
Adrenal Gland Neoplasms/physiopathology , Aortic Bodies , Paraganglioma, Extra-Adrenal/diagnosis , Paraganglioma, Extra-Adrenal/surgery , Pheochromocytoma/physiopathology , Syncope/physiopathology , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/surgery , Adult , Humans , Male , Middle Aged , Pheochromocytoma/diagnosis , Pheochromocytoma/surgery , Tropical Climate , Vasodilation
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