Analysis of ALK-status of tumor tissue in patients with non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC).

Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. Patients and Methods From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate. Results Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02). Conclusion Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.

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RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-012-1834-x ◽

2012 ◽

Vol 69 (5) ◽

pp. 1277-1287 ◽

Cited By ~ 19

Author(s):

Guo Bing Zhang ◽

Jian Chen ◽

Lin Run Wang ◽

Jun Li ◽

Ming Wei Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Tumor Tissue ◽

Small Cell ◽

Small Cell Lung ◽

Ercc1 Expression

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CD1c+ and CD303+ dendritic cells in peripheral blood, lymph nodes and tumor tissue of patients with non-small cell lung cancer

Oncology Reports ◽

10.3892/or.19.1.237 ◽

2008 ◽

Cited By ~ 3

Author(s):

Jacek Tabarkiewicz ◽

Pawel Rybojad ◽

Andrzej Jablonka ◽

Jacek Rolinski

Keyword(s):

Lung Cancer ◽

Dendritic Cells ◽

Lymph Nodes ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Tumor Tissue ◽

Small Cell ◽

Small Cell Lung

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Comparison of cytokeratin 19 expression in tumor tissue and serum CYFRA 21-1 levels in non‑small cell lung cancer

Polish Archives of Internal Medicine ◽

10.20452/pamw.598 ◽

2009 ◽

Vol 119 (1-2) ◽

pp. 33-38

Author(s):

Monika Kosacka ◽

Renata Jankowska

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tumor Tissue ◽

Small Cell ◽

Cytokeratin 19 ◽

Small Cell Lung

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Fibroblast kinase 1-3 inhibitor BGJ398 in patients with FGFR1 amplified squamous non-small cell lung cancer treated in a phase I study: Evaluation of tumor tissue and response at a single center.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20664 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20664-e20664

Author(s):

Lucia Nogova ◽

Florian Malchers ◽

Elisabeth Bitter ◽

Sebastian Yves Friedrich Michels ◽

Rieke Nila Fischer ◽

...

Keyword(s):

Lung Cancer ◽

Phase I ◽

Small Cell Lung Cancer ◽

Ct Scan ◽

Cell Lung Cancer ◽

Phase I Study ◽

Tumor Tissue ◽

Small Cell ◽

Small Cell Lung ◽

Pik3ca Mutations

e20664 Background: Fibroblast growth factor receptor 1 ( FGFR1) amplification in squamous cell non-small cell lung cancer (sqNSCLC) has been described as potential oncogenic and targetable driver in cell lines and murine models. However, a phase I study evaluating FGFR 1-3 inhibitor BGJ398 showed moderate response rate of 11% in FGFR1amplified sgNSCLC treated with dose ≥ 100mg. To identify underlying mechanisms of resistance, we analyzed tumor tissues of selected patients. Methods: Within the phase I BGJ398 study, patients (pts) with FGFR1amplified sqNSCLC were treated orally with escalating dose (5 to 150mg) of BGJ398 once daily (QD) or 50mg twice a day. In the expansion phase, pts received BGJ398 either continuously QD or on a 3-weeks on/1-week off schedule. CT scans for response were performed every 8 weeks. Available tumor tissue of pts treated with BGJ398 at our center was analyzed using hybrid capture–based massively parallel sequencing (CAGE). Results: Twenty-one pts with FGFR1 amplified sqNSCLC were treated with ≥ 100mg BGJ398 at our site. As best response, 3 pts showed partial response (PR), 7 pts stable disease (SD) and 7 pts progressive disease (PD). Two pts withdrew their consents and 2 pts died ahead of first CT scan: one due to infection and one due to sudden death. We performed CAGE covering 256 genes on 9 patients: on 3 pts with PR, 2 pts with SD, 2 pts with PD and 2 pts who died before first CT scan. All analyzed patients harbored mutations in TP53. Additionally, we detected two CDKN2A (one patient with PR and one patient who died before first CT) and three MLL2 stop codon and frame shift mutations (two patients with SD and one patient with PD). Of interest, we identified three patients with two canonical (one patient with SD and one patient who died before first CT) and one non-canonical mutations in PIK3CA(one patient with SD). Conclusions: In our analysis, MLL2 and PIK3CA mutations seem to have a negative impact on response in FGFR1 amplified pts treated with BGJ398. Further analysis with higher patient number is needed to identify the role of MLL2 and PIK3CA mutations in FGFR1 amplified sqNSCLC. Clinical trial information: NCT01004224.

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