New Strategies in Non–Small Cell Lung Cancer: Improving Outcomes in Chemoradiotherapy for Locally Advanced Disease

Rengan, Ramesh; Maity, Amit; Stevenson, James P.; Hahn, Stephen M.

doi:10.1158/1078-0432.ccr-10-2760

Cited by 13 publications

(11 citation statements)

References 82 publications

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“…All potential prognostic factors were transformed into categorical variables. The patients were grouped as male vs. female, squamous vs. non-squamous cell carcinoma, neutrophil count >7,000 vs. ≤7,000̸mm 3 (upper limit of normal), lymphocyte count ≥1,100 vs. <1,100̸mm 3 (lower limit of normal), monocyte count >600 vs. ≤600̸mm 3 (upper limit of normal), platelet count >350x10 3 vs. ≤350x10 3 ̸mm 3 (upper limit of normal), NLR <5 vs. ≥5 (ratio between neutrophil and lymphocyte counts at baseline) and platelet-to-lymphocyte ratio (PLR) <300 vs. ≥300 (ratio between platelet and lymphocyte counts at baseline). The cut-off values of PLR and NLR were determined as previously described (17).…”

Section: Discussionmentioning

confidence: 99%

“…Concurrent chemoradiotherapy (CCRT) is the standard treatment strategy for locally advanced non-resectable non-small-cell lung cancer (NSCLC) (2). However, the clinical outcome is disappointing, with a 5-year survival rate of only ~20% (range, 15-40%) (3,4). Recently, combined treatment with anti-angiogenic therapy and chemotherapy or radiotherapy has shown a survival advantage (5).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic performance of inflammation-based prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy

Tang

Peng

et al. 2016

Molecular and Clinical Oncology

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Abstract.A proportion of patients with locally advanced nonsmall-cell lung cancer (NSCLC) may benefit from anti-angiogenic therapy combined with concurrent chemoradiotherapy; however, effective prognostic biomarkers are required for prognosis. In this study, we aimed to establish whether inflammation-based factors offer a prognostic benefit in terms of response rate (RR) and overall survival (OS) in stage III NSCLC patients treated by Endostar with concurrent chemoradiotherapy (CCRT). We retrospectively investigated an unselected cohort of stage III NSCLC patients, who were treated by combined Endostar and CCRT. The log-rank test was used to analyze the association between each clinical variable and OS. Cox regression models were fitted to identify risk factors associated with OS. A total of 82 patients with stage III NSCLC were treated with a combination of Endostar and CCRT and 78 patients were included in the data analysis. A total of 13 patients achieved a complete response, 49 achieved a partial response, 6 had stable disease, 8 had progressive disease and 2 patients could not be evaluated. The median progression-free survival of the entire group was 10.50 months (95% CI: 6.298-14.702), while the median OS was 22.83 months (95% CI: 19.156-26.504). On χ 2 test analysis, the neutrophil-to-lymphocyte ratio (NLR) exerted a significant effect on RR (P=0.048). The univariate analysis identified the factors associated with OS, including NLR (P=0.004) and monocyte count (P=0.001), whereas the multivariate analysis confirmed NLR [P=0.043, hazard ratio (HR)=0.502] and monocyte count (P=0.011, HR=0.387) as independent prognostic factors for OS. Our results indicated that, in patients with stage III NSCLC treated by a combination of Endostar and CCRT, pre-treatment elevated NLR and monocyte number are negatively associated with OS. IntroductionLung cancer is the most common type of cancer worldwide (1). Concurrent chemoradiotherapy (CCRT) is the standard treatment strategy for locally advanced non-resectable non-small-cell lung cancer (NSCLC) (2). However, the clinical outcome is disappointing, with a 5-year survival rate of only ~20% (range, 15-40%) (3,4). Recently, combined treatment with anti-angiogenic therapy and chemotherapy or radiotherapy has shown a survival advantage (5). Among all anti-angiogenic drugs, recombinant human endostatin (Endostar), when administered with traditional CRT in patients with locally advanced NSCLC, showed promising results (6-10). We previously conducted a phase II clinical trial of endostatin combined with CCRT in patients with locally advanced NSCLC, achieving improved local control and survival rate (11). However, previous research has demonstrated that not all patients benefit from anti-angiogenic therapy (11). Thus, suitable case selection for Endostar treatment is crucial to avoid excessive medical treatment.It has been demonstrated that inflammation-mediated interaction between endothelial cells and the innate immune system plays an important role in resistance to anti-angiogen...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic performance of inflammation-based prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy

Tang

Peng

et al. 2016

Molecular and Clinical Oncology

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“…1 Even with aggressive therapy, lung cancer patients with locally advanced disease who are not surgically resectable on the basis of the extent of the primary disease or regional nodal involvement, have an extremely poor long-term survival, in the order of 15 to 40%. 2 Despite improvement with combined modality therapy, both local control and survival still remain poor. 2 These facts have led researcher to investigate other possible mechanism that may play role in the progression of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

“…2 Despite improvement with combined modality therapy, both local control and survival still remain poor. 2 These facts have led researcher to investigate other possible mechanism that may play role in the progression of lung cancer. In recent years cancer stem cells (CSC) have emerged as the focus of intense investigations in cancer research.…”

Section: Introductionmentioning

confidence: 99%

Lung cancer stem cells: Tumor biology and clinical implications

Nurwidya

Murakami

Takahashi

et al. 2012

Asia-Pac J Clncl Oncology

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The concept of cancer stem cells (CSC) has drawn great attention from researchers in both molecular and clinical fields as has brought a new perspective to the way we manage cancer. CSC have several characteristics that are shared by the properties of normal stem cells, such as differentiation, self-renewal and homeostatic control. However, CSC have the capacity to both divide and expand the CSC pool and to differentiate into heterogeneous non-tumorigenic cancer cells. Even more, CSC have an inherent high resistance to chemotherapeutic agents that leads to recurrence and poor long-term survival, especially in lung cancer patients. CSC-targeting agents are now undergoing in vitro and in vivo studies, some of which have provided promising results for further clinical studies setting. In this article we review the concept of CSC from the perspective of tumor biology, including the origin of CSC and its biomarkers. As lung cancer is the leading cause of cancer-related deaths worldwide, we focus on the properties and clinical implications of lung CSC.

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“…1,2 Despite recent technical advances in radiation therapy, incidental irradiation that damages normal lung tissue in the path of the radiation beam remains unavoidable and frequently results in radiation-induced lung injury (RILI). 3 As such, this deleterious pulmonary effect not only compromises quality of life for a subset of long-term cancer survivors but also represents a major dose-limiting factor in radiation therapy.…”

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confidence: 99%

Radiation-Induced Impairment in Lung Lymphatic Vasculature

Cui

Wilder

Rietz

et al. 2014

Lymphatic Research and Biology

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Background: The lymphatic vasculature has been shown to play important roles in lung injury and repair, particularly in lung fibrosis. The effects of ionizing radiation on lung lymphatic vasculature have not been previously reported. Methods and Results: C57Bl/6 mice were immobilized in a lead shield exposing only the thoracic cavity, and were irradiated with a single dose of 14 Gy. Animals were sacrificed and lungs collected at different time points (1, 4, 8, and 16 weeks) following radiation. To identify lymphatic vessels in lung tissue sections, we used antibodies that are specific for lymphatic vessel endothelial receptor 1 (LYVE-1), a marker of lymphatic endothelial cells (LEC). To evaluate LEC cell death and oxidative damage, lung tissue sections were stained for LYVE-1 and with TUNEL staining, or 8-oxo-dG respectively. Images were imported into ImageJ v1.36b and analyzed. Compared to a non-irradiated control group, we observed a durable and progressive decrease in the density, perimeter, and area of lymphatic vessels over the study period. The decline in the density of lymphatic vessels was observed in both subpleural and interstitial lymphatics. Histopathologically discernible pulmonary fibrosis was not apparent until 16 weeks after irradiation. Furthermore, there was significantly increased LEC apoptosis and oxidative damage at one week post-irradiation that persisted at 16 weeks. Conclusions: There is impairment of lymphatic vasculature after a single dose of ionizing radiation that precedes architectural distortion and fibrosis, suggesting important roles for the lymphatic circulation in the pathogenesis of the radiation-induced lung injury.

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New Strategies in Non–Small Cell Lung Cancer: Improving Outcomes in Chemoradiotherapy for Locally Advanced Disease

Cited by 13 publications

References 82 publications

Prognostic performance of inflammation-based prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy

Prognostic performance of inflammation-based prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy

Lung cancer stem cells: Tumor biology and clinical implications

Radiation-Induced Impairment in Lung Lymphatic Vasculature

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