Biomarkers for efficacy of adjuvant chemotherapy following complete resection in NSCLC stages I–IIIA

Wallerek, Sandra; Sørensen, Jens Benn

doi:10.1183/16000617.00005814

Cited by 27 publications

(30 citation statements)

References 76 publications

(94 reference statements)

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“…Stage I patients usually receive surgical resection only because platinum-based adjuvant chemotherapy (ACT) has not shown to be beneficial for IA patients (Crino et al , 2015) and controversial for IB patients (Tsuboi et al , 2007). Stage II–IIIA patients usually receive platinum-based ACT after surgical resection, but only 4–15% survival benefit after ACT has been observed (Wallerek and Sorensen, 2015). Heterogeneity of response to platinum-based ACT significantly confounds treatment of LUAD patients.…”

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confidence: 99%

An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

Qin

et al. 2016

Br J Cancer

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Background:For lung adenocarcinoma (LUAD) patients receiving platinum-based adjuvant chemotherapy (ACT), predictive signatures extracted from survival data solely are not directly associated with platinum response. Another limitation of reported signatures, commonly based on risk scores summarised from gene expressions, is that they could not be applied directly to samples measured by different laboratories due to experimental batch effects.Methods:Using 60 samples of LUAD patients receiving platinum-based ACT in TCGA, we pre-selected gene pairs whose within-samples relative expression orderings (REOs) were significantly associated with both pathological response and 5-year survival, from which we selected an optimal signature whose within-samples REOs could identify responders with improved 5-year survival rate.Results:A predictive signature consisting of three gene pairs was developed. In an independent data set integrated from five small data sets, the predicted responders had a significantly higher 5-year survival rate than the predicted non-responders if and only if they received platinum-based ACT (log-rank P=0.0006). The predicted responders showed a 22% absolute benefit of platinum-based ACT in 5-year survival rate compared with untreated patients (log-rank P=0.0019).Conclusions:The REO-based signature can individually predict response to platinum-based ACT with concordant survival benefit directly for LUAD samples measured by different laboratories.

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confidence: 99%

An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

Qin

et al. 2016

Br J Cancer

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“…Thus, patients are selected by using biomarkers that predict prognosis [33]. Adjuvant chemotherapy is prescribed only to the selected patients who are likely to benefit from the treatment [34, 35]. The outcomes have showed that high Orai3 expression was associated with poor prognostic for MFS in Ib stage and with poor prognosis for OS in II-III stage.…”

Section: Discussionmentioning

confidence: 99%

Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

et al. 2016

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Orai3 channel has emerged as important player in malignant transformation. Indeed, its expression is increased in cancer and favors cell proliferation and survival by permitting calcium influx. In this study, Orai3 was overexpressed in lung adenocarcinoma as compared to their matched non-tumour samples and was associated with tumoural aggressiveness. Moreover, its expression was associated with estrogen receptor alpha (ERα) expression and visceral pleural invasion in multivariate analysis. Furthermore, both the overall survival (OS) median and the metastasis free survival (MFS) median of tumors with high Orai3 expression were lower than in low Orai3 expression regardless of cancer stage (35.01 months vs. 51.11 months for OS and 46.01 months vs. 62.04 months for MFS). In conclusion, Orai3 protein level constitutes an independent prognostic marker in lung adenocarcinoma, and a novel prognostic marker that could help selecting the patients with worst prognosis to be treated with adjuvant chemotherapy in resectable stage.

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“…Recently, individualized medication has served an important role in improving chemotherapeutic outcomes, since the effects of anti-cancer drugs are different among individuals. For instance, individualized chemotherapy regimens for NSCLC are often selected on the basis of a number of chemosensitivity-associated biomarkers, including epidermal growth factor receptor (EGFR) mutation status ( 9 ), anaplastic lymphoma kinase (ALK) gene rearrangement status ( 10 ), excision repair cross-complementation group 1 (ERCC1) status ( 11 ), ribonucleotide reductase regulatory subunit M1 (RRM1) ( 12 ), class III β-tubulin ( 13 , 14 ), and so on ( 15 ). Several recent clinical studies have indicated that such biomarkers may help us to identify subsets of patients that would benefit from adjuvant chemotherapy ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, Kawamura et al ( 22 ) used this test to select the most appropriate chemotherapy regimens for patients with advanced NSCLC. Of course, there have also been numerous studies in which this test was used to aid the treatment of malignancies other than NSCLC, indicating that the CD-DST may provide useful information that would aid the development of individualized chemotherapy for patients with various types of malignant disease ( 16 – 21 ); for example, it could be used to provide information about chemosensitivity-associated biomarkers such as those described above ( 9 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection

Akazawa

Higashiyama

Nishino

et al. 2017

Molecular and Clinical Oncology

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The impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non-small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in patients with p (pathology)-stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum-based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled. Their surgical specimens were subjected to the CD-DST. The patients were subsequently classified into two groups on the basis of in vitro anti-cancer drug sensitivity data obtained using the CD-DST: The sensitive group (25 patients) were treated with regimens including one or two of the anti-cancer drug(s) that were indicated to be effective by the CD-DST, whereas the non-sensitive group (14 patients) were treated with chemotherapy regimens that did not include any CD-DST-selected anti-cancer drugs. There were no significant differences in the background characteristics of the two groups [including in respect of the pathological TN (tumor-lymph node) stage, tumor histology, epidermal growth factor receptor mutation status, the frequency of each chemotherapy regimen, and the number of administered cycles]. The 5-year disease-free survival (DFS) rate of the sensitive group was 32.3%, whereas that of the non-sensitive group was 14.3% (P=0.037). In contrast, no difference in overall survival (OS) was observed (P=0.76). Multivariate analysis revealed that adjuvant chemotherapy based on the CD-DST had a significant favorable effect on the DFS (P=0.01). Therefore, the present study has demonstrated that CD-DST data obtained from surgical specimens aid the selection of effective platinum-based adjuvant chemotherapy regimens for patients undergoing complete resection for p-stage IIIA NSCLC. The use of CD-DST-guided platinum-based regimens may have a beneficial impact on the DFS of such patients.

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Biomarkers for efficacy of adjuvant chemotherapy following complete resection in NSCLC stages I–IIIA

Cited by 27 publications

References 76 publications

An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection

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