Dataset Information

Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

ABSTRACT: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, in patients with non-small cell lung cancer (NSCLC). However, humoral immune responses to EGFR in NSCLC patients have not been well studied. In this study, we investigated the clinical significance of immunoglobulin G (IgG) responses to EGFR-derived peptides in NSCLC patients receiving gefitinib. Plasma IgG titers to each of 60 different EGFR-derived 20-mer peptides were measured by the Luminex system in 42 NSCLC patients receiving gefitinib therapy. The relationships between the peptide-specific IgG titers and presence of EGFR mutations or patient survival were evaluated statistically. IgG titers against the egfr_481-500, egfr_721-740, and egfr_741-760 peptides were significantly higher in patients with exon 21 mutation than in those without it. On the other hand, IgG titers against the egfr_841-860 and egfr_1001-1020 peptides were significantly lower and higher, respectively, in patients with deletion in exon 19. Multivariate Cox regression analysis showed that IgG responses to egfr_41_ 60, egfr_61_80 and egfr_481_500 were significantly prognostic for progression-free survival independent of other clinicopathological characteristics, whereas those to the egfr_41_60 and egfr_481_500 peptides were significantly prognostic for overall survival. Detection of IgG responses to EGFR-derived peptides may be a promising method for prognostication of NSCLC patients receiving gefitinib. Our results may provide new insight for better understanding of humoral responses to EGFR in NSCLC patients.

SUBMITTER: Azuma K

PROVIDER: S-EPMC3909003 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

Azuma Koichi K Komatsu Nobukazu N Hattori Satoshi S Matsueda Satoko S Kawahara Akihiko A Sasada Tetsuro T Itoh Kyogo K Hoshino Tomoaki T

PloS one 20140131 1

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, in patients with non-small cell lung cancer (NSCLC). However, humoral immune responses to EGFR in NSCLC patients have not been well studied. In this study, we investigated the clinical significance of immunoglobulin G (IgG) responses to EGFR-derived peptides in NSCLC patients receiving gefitinib. Plasma IgG titers to each of 60 ...[more]

PMID: 24497964

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Project description:ObjectivesThis study aims to establish nomograms to accurately predict the overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who received chemotherapy alone as the first-line treatment.Materials and methodsIn a training cohort of 121 NSCLC patients, radiomic features were extracted, selected from intra- and peri-tumoral regions, and used to build signatures (S1 and S2) using a Cox regression model. Deep learning features were obtained from three convolutional neural networks and utilized to build signatures (S3, S4, and S5) that were stratified into over- and under-expression subgroups for survival risk using X-tile. After univariate and multivariate Cox regression analyses, a nomogram incorporating the tumor, node, and metastasis (TNM) stages, radiomic signature, and deep learning signature was established to predict OS and PFS, respectively. The performance was validated using an independent cohort (61 patients).ResultsTNM stages, S2 and S3 were identified as the significant prognosis factors for both OS and PFS; S2 (OS: (HR (95%), 2.26 (1.40-3.67); PFS: (HR (95%), 2.23 (1.36-3.65)) demonstrated the best ability in discriminating patients with over- and under-expression. For the OS nomogram, the C-index (95% CI) was 0.74 (0.70-0.79) and 0.72 (0.67-0.78) in the training and validation cohorts, respectively; for the PFS nomogram, the C-index (95% CI) was 0.71 (0.68-0.81) and 0.72 (0.66-0.79). The calibration curves for the 3- and 5-year OS and PFS were in acceptable agreement between the predicted and observed survival. The established nomogram presented a higher overall net benefit than the TNM stage for predicting both OS and PFS.ConclusionBy integrating the TNM stage, CT radiomic signature, and deep learning signatures, the established nomograms can predict the individual prognosis of NSCLC patients who received chemotherapy. The integrated nomogram has the potential to improve the individualized treatment and precise management of NSCLC patients.

Project description:BackgroundOverall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification).MethodsWe extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype.Results20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies.ConclusionsOur study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

Dataset Information

Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

Publications

Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

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