Mass Spectrometry to Classify Non–Small-Cell Lung Cancer Patients for Clinical Outcome After Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Multicohort Cross-Institutional Study

Taguchi, Fumiko; Solomon, Benjamin; Gregorc, Vanesa; Röder, Heinrich; Gray, Robert J.; Kondo, Kazuo; Nishio, Makoto; Brahmer, Julie R.; Spreafico, Anna; Ludovini, Vienna; Massion, Pierre P.; Dziadziuszko, Rafał; Schiller, Joan H.; Grigorieva, Julia; Tsypin, Maxim; Hunsucker, Stephen W.; Caprioli, Richard M.; Duncan, Mark W.; Hirsch, Fred R.; Bunn, Paul A.; Carbone, David P.

doi:10.1093/jnci/djk195

Cited by 290 publications

(297 citation statements)

References 28 publications

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“…Secondly, in the present study, patients with wild-type EGFR and no EGFR-TKI therapy were more likely to be smokers and to have brain metastasis and adrenal gland metastasis than those with wild-type EGFR and EGFR-TKI therapy. Finally, the response rate of EGFR-TKI therapy in patients with wild-type EGFR was 10-20% in previous reports [8,12,32,47,48].…”

Section: Discussionmentioning

confidence: 80%

Survival of lung adenocarcinoma patients with malignant pleural effusion

Tsai

et al. 2012

Eur Respir J

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In the era of targeted therapy, the association between lung adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of lung adenocarcinoma patients with MPE.From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed.We collected MPEs from 448 patients in stage IV lung adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p50.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p50.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p50.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV lung adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.

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Section: Discussionmentioning

confidence: 80%

Survival of lung adenocarcinoma patients with malignant pleural effusion

Tsai

et al. 2012

Eur Respir J

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“…Further, in complex mass spectra, peak widths can be influenced by the presence of proximate peaks and the peak picking and the peak intensity measurement process must take these local effects into account. With rigorous spectral pre-processing consisting of regional (in terms of m/z) background determinations and noise estimation, alignment using common peaks in training sample sets and normalization methods using partial ion current techniques, MALDI mass spectra are highly reproducible across laboratories and even across slightly different hardware [22].…”

Section: Data Analysis: Special Considerations In Profilingmentioning

confidence: 99%

“…We recently reported a study that establishes the reproducibility of the profiling approach both within and between laboratories. We developed and tested the ability of a predictive algorithm based on MALDI-TOF MS analysis of pre-treatment serum to identify patients who are likely to benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) [22]. Some but not all patients with non-small cell lung cancer (NSCLC) respond to treatment with EGFR TKIs.…”

Section: Protein Profiling Studiesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

195

162

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This review summarizes the essential characteristics of matrix-assisted laser desorption/ionization (MALDI) timeof-flight mass spectrometry (TOF MS), especially as they relate to its applications in quantitative analysis. Approaches to quantification by MALDI-TOF MS are presented and published applications are critically reviewed.Keywords: quantification; quantitative analysis; MALDI; mass spectrometry; biomarkers OVERVIEWSince its inception in 1987 [1], matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS) has been applied for the analysis of a wide range of biomolecules. Initial applications were almost exclusively for the qualitative analysis of biopolymers because MALDI-TOF MS provided a fast and accurate approach to molecular mass and purity information: Is my material the right mass and is it free from contaminants? Because of the speed of analysis, ease of use, relative low equipment cost, ease of data interpretation and limited potential for cross-contamination between samples/users, MALDI-TOF MS systems were considered walk-up instruments where investigators run their own samples and determine, within minutes, whether they were on the right track with their work.There were, however, two specific areas of application where MALDI-TOF MS was initially viewed as impractical: i.e. the analysis of low mass analytes and quantitative applications. Low mass analysis is complicated by the vast molar excess of the matrix that can swamp any analyte-specific signal in the low m/z region of the spectrum. Quantitative analysis was viewed as implausible because crystallization does not yield a uniform distribution of the analyte and matrix across the target surface and this gives rise to regions where the analyte signal is especially intense relative to other locations on the target surface. MALDI MS was therefore viewed as inherently irreproducible because, for a given amount of analyte loaded onto the target, the measured ion intensity varies.Subsequently, it has been shown that both these perceived limitations can be overcome and quantification can be routine, both for low and high mass analytes. Now, an extensive list of published applications includes quantification of amino acids, lipids, natural products, drugs, polymers, herbicides, metabolites, toxins, oligonucleotides, carbohydrates, peptides and proteins. (Selected applications from these areas are discussed at the end of this review.) Here, we focus on the quantitative applications of MALDI and illustrate applications relating to both low and high-molecular mass analytes. We also discuss the strategies for applying MALDI to relative and absolute quantification. While MALDI is most commonly combined with TOF analysers, other analyser options are possible and applications employing these are also presented. Our aim is not to provide an exhaustive catalogue of published applications, but to discuss the general principles and to illustrate the

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“…This technology has already been used to characterize diagnostic and prognostic markers in tumors such as breast (74), brain (75), colon (76), gastric (77), lung (78)(79)(80), and prostate cancer (81). In a large retrospective study by Taguchi et al, blood collected from patients with NSCLC before treatment with an EGFR TKI was analyzed by MALDI IMS and compared against patient outcome, and an algorithm was developed to stratify patients into "good" or "poor" risk groups based on possible clinical benefit from EGFR TKI treatment (82). Subsequently, the large phase 3 PROSE trial was able to prospectively demonstrate that patients with NSCLC carrying a good proteomic test classification predicted for benefit with erlotinib therapy over chemotherapy, whereas those with a poor proteomic classification predicted for benefit with chemotherapy over erlotinib (83).…”

Section: Future Technologies For Tumor Characterization Of Ctcsmentioning

confidence: 99%

Biophysical technologies for understanding circulating tumor cell biology and metastasis

Nieva

2017

Transl. Lung Cancer Res.

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An understanding of cancer evolution in lung cancer with its associated resistance to therapy can only be achieved with repeated sampling and analysis of the cancer. Given the high risks and costs associated with repeat physical biopsy, alternative technologies must be applied. Several modalities exist for analysis and re-analysis of cancer biology. Among them are the CellSearch platform, the CTC chip, and the highdefinition CTC platform. While the former is primarily able to provide prognosticating information in the form of CTC enumeration, the latter two have the advantage of serving as a platform to study tumor biology. Techniques for analysis of single cell genomics, as well as protein expression on a single cell basis provide scientists with the capacity to understand cancer cell populations as a collection of individual cells, rather than as an average of all cells. A multimodal combination of circulating tumor DNAs (ctDNAs), CTCs, proteomics, and CTC-derived xenografts (CDXs) to create computational models useful in diagnosis, prognostication, and predictiveness to treatment is likely the future of tailoring individualized cancer care.

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Mass Spectrometry to Classify Non–Small-Cell Lung Cancer Patients for Clinical Outcome After Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Multicohort Cross-Institutional Study

Abstract: This MALDI MS algorithm was not merely prognostic but could classify NSCLC patients for good or poor outcomes after treatment with EGFR TKIs. This algorithm may thus assist in the pretreatment selection of appropriate subgroups of NSCLC patients for treatment with EGFR TKIs.

Cited by 290 publications

References 28 publications

Survival of lung adenocarcinoma patients with malignant pleural effusion

Survival of lung adenocarcinoma patients with malignant pleural effusion

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Biophysical technologies for understanding circulating tumor cell biology and metastasis

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