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Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.

ABSTRACT: The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort.ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis.

SUBMITTER: Doebele RC

PROVIDER: S-EPMC3370097 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.

Doebele Robert C RC Lu Xian X Sumey Christopher C Maxson Delee A DA Weickhardt Andrew J AJ Oton Ana B AB Bunn Paul A PA Barón Anna E AE Franklin Wilbur A WA Aisner Dara L DL Varella-Garcia Marileila M Camidge D Ross DR

Cancer 20120126 18

<h4>Background</h4>The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.<h4>Methods</h4>A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 ...[more]

PMID: 22282022

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Project description:BackgroundTo compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma.Materials and methodsWe developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed.ResultsIn terms of testing costs, tissue-first approach incurred US$2,354($1,963-$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010-$5,480), $6,778 ($5,923-$7,600), and $7,006 ($6,047-$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively.ConclusionThe tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.

Project description:Solid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Up to 10% of patients with localized disease at presentation will develop systemic metastases, usually in the peritoneum or the liver. Due to the rarity of SPNs and the overall excellent prognosis, reliable prognostic factors to predict malignant biological behavior remain undetermined. Therefore, we aimed to define clinical, histological, and microRNA patterns that are associated with metastatic disease. We conducted a retrospective single center study on all patients operated for SPN of pancreas between 1995 and 2018. Clinical and pathological data were collected, and expression patterns of 2578 human microRNAs were analyzed using microRNA array (Affimetrix 4.1) in normal pancreases (NPs), localized tumors (LTs), and metastatic tumors (MTs). The diagnosis of SPN was confirmed in 35 patients who included 28 females and 3 males, with a mean age of 33.8 ± 13.9 years. The only clinical factor associated with metastases was tumor size (mean tumor size 5.20 ± 3.78 in LT versus 8.13± 1.03 in MT, p < 0.012). Microscopic features of malignancy were not associated with metastases, nor were immunohistochemical stains, including the proliferative index KI67. Higher expressions of miR-184, miR-10a, and miR-887, and lower expressions of miR-375, miR-217, and miR-200c were observed in metastatic tissues on microarray, and validated by real-time polymerase chain reaction. Hierarchal clustering demonstrated that the microRNA expression pattern of MTs was significantly different from that of LTs. The only clinical factor associated with metastases of SPN of pancreas was tumor size. Histological features and immunohistological staining were not predictive of metastases. A panel of six microRNAs was differentially expressed in MTs, and these findings could potentially be used to predict tumor behavior. Validation of these results is needed in larger series.

Dataset Information

Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.

Publications

Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer.

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