Predicting the sites of metastases from lung cancer using molecular biologic markers

D’Amico, Thomas A.; Aloia, Thomas A.; Moore, Mary B.; Conlon, Debbi H.; Herndon, James E.; Kinch, Michael S.; Harpole, David H.

doi:10.1016/s0003-4975(01)02979-4

Cited by 68 publications

(40 citation statements)

References 19 publications

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“…Patients with early stage NSCLC who developed isolated brain metastases had a significantly higher expression of molecular markers, such as p53 and urokinase plasminogen activator, and a lower expression of E-cadherin by immunohistochemical analysis. 47 A similar study from the Brigham and Women's Hospital (Boston, Mass) also demonstrated that immunohistochemical markers, including Ki-67, caspase-3, VEGF-C, and E-cadherin, may be able to predict patients at higher risk of developing brain metastases. 48 Recently, genomic signatures of malignancies are being exploited to better understand prognosis and to identify patients who may benefit from further intervention.…”

Section: Biological Predictorsmentioning

confidence: 90%

Factors associated with the development of brain metastases

Hubbs

Boyd

Hollis

et al. 2010

Cancer

120

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BACKGROUND The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors. METHODS The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases. RESULTS Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases. CONCLUSIONS In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk. Cancer 2010;116:5038-46.

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Section: Biological Predictorsmentioning

confidence: 90%

Factors associated with the development of brain metastases

Hubbs

Boyd

Hollis

et al. 2010

Cancer

120

View full text Add to dashboard Cite

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“…Until the results of ongoing studies attempting to correlate molecular biomarkers and gene products with clinical outcome in patients treated with neoadjuvant therapy for locally advanced NSCLC become applicable, it appears feasible to use pCR as a means of identifying patients who have a low enough risk of extracranial disease recurrence to benefit from vigilant surveillance or PCI. [30][31][32] The fact that 7 of 51 of patients experienced local-regional failure and an additional 6 of 51 had extracranial distant failure after pCR, however, suggests that pCR is neither a surrogate for complete remission nor an entirely accurate predictor of disease response to therapy.…”

Section: Discussionmentioning

confidence: 99%

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

Chen

Jahan

Jablons

et al. 2007

Cancer

127

100

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BACKGROUND. The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall‐cell lung cancer (NSCLC). METHODS. Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI). RESULTS. Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty‐two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5‐year estimates of brain metastasis‐free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively. CONCLUSION. Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed. Cancer 2007. © 2007 American Cancer Society.

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“…1,5,6 For oncology applications, interest in EphA2 has grown recently due to its increased expression in most cancers including lung, breast, ovary, prostate, colorectal, skin and esophagus. [7][8][9][10][11][12][13] Interestingly, EphA2 is located on chromosome 1p36.1, which is a hotspot for rearrangements in many human cancers including ovarian cancer. [14][15][16] We have previously demonstrated that EphA2 is overexpressed in 76% of epithelial ovarian cancers.…”

Section: Introductionmentioning

confidence: 99%

EphA2 overexpression promotes ovarian cancer growth

Lü

Shahzad

Wang

et al. 2008

Cancer Biology & Therapy

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Background: Silencing EphA2 has been shown to result in anti-tumor efficacy. However, it is not known whether increasing EphA2 expression specifically results in increased tumor growth and progression. We examined the effects of stable EphA2 transfection into poorly invasive ovarian cancer cells with regard to in vitro invasive and in vivo metastatic potential.Results: In low cell density, EphA2-overexpressing A2780 cells (A2780-EphA2) displayed less cell-cell contact, increased cell-extracellular matrix (ECM) attachment and anchorage-independent cell growth compared to empty vector controls. There was no significant effect on anchorage-dependent cell proliferation, migration or invasion. Increased expression of EphA2 promoted tumor growth and enhanced the metastatic potential in A2780-EphA2 human ovarian cancer xenografts. The overexpression of EphA2 resulted in enhanced microvessel density (MVD), but had no effect on tumor cell proliferation.Methods: EphA2 gene was introduced into A2780 cells by retroviral infection. The effects of increased EphA2 expression were examined on cellular morphology, and anchorage-dependent and independent cell growth. Furthermore, the effect of EphA2 overexpression on metastatic ability was determined using an orthotopic nude mouse model of ovarian carcinoma.Conclusions: EphA2 promotes tumor growth by enhancing cell-ECM adhesion, increasing anchorage-independent growth and promoting angiogenesis.

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Predicting the sites of metastases from lung cancer using molecular biologic markers

Cited by 68 publications

References 19 publications

Factors associated with the development of brain metastases

Factors associated with the development of brain metastases

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

EphA2 overexpression promotes ovarian cancer growth

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