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Published in: Strahlentherapie und Onkologie 3/2014

01-03-2014 | Original article

A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer

Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor

Authors: C. Ostheimer, M. Bache, A. Güttler, M. Kotzsch, D. Vordermark

Published in: Strahlentherapie und Onkologie | Issue 3/2014

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Abstract

Background

Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy.

Material and methods

Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated.

Results

All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV.

Conclusion

This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.
Literature
1.
go back to reference Höckel M, Vaupel P (2001) Biological consequences of tumor hypoxia. Semin Oncol 28:6–41CrossRef Höckel M, Vaupel P (2001) Biological consequences of tumor hypoxia. Semin Oncol 28:6–41CrossRef
2.
3.
go back to reference Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239PubMedCrossRef Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239PubMedCrossRef
4.
go back to reference Zips D, Böke S, Kroeber T et al (2011) Prognostic value of radiobiological hypoxia during fractionated irradiation for local tumor control. Strahlenther Onkol 187:306–310PubMedCrossRef Zips D, Böke S, Kroeber T et al (2011) Prognostic value of radiobiological hypoxia during fractionated irradiation for local tumor control. Strahlenther Onkol 187:306–310PubMedCrossRef
5.
go back to reference Vaupel P, Kelleher DK, Höckel M (2001) Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 28:29–35PubMedCrossRef Vaupel P, Kelleher DK, Höckel M (2001) Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 28:29–35PubMedCrossRef
6.
go back to reference Ostheimer C, Vordermark D (2013) Osteopontin—an indicator of tumor hypoxia and treatment resistance. In: Vordermark D (ed) Hypoxia: causes, types and management. Nova Publishers, New York Ostheimer C, Vordermark D (2013) Osteopontin—an indicator of tumor hypoxia and treatment resistance. In: Vordermark D (ed) Hypoxia: causes, types and management. Nova Publishers, New York
7.
go back to reference Vordermark D, Brown JM (2003) Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? Strahlenther Onkol 179:801–811PubMedCrossRef Vordermark D, Brown JM (2003) Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? Strahlenther Onkol 179:801–811PubMedCrossRef
8.
go back to reference Le QT (2007) Identification and targeting hypoxia in head and neck cancer—a brief overview of current approaches. Int J Radiat Oncol Biol Phys 69:S56–S58PubMedCentralPubMedCrossRef Le QT (2007) Identification and targeting hypoxia in head and neck cancer—a brief overview of current approaches. Int J Radiat Oncol Biol Phys 69:S56–S58PubMedCentralPubMedCrossRef
9.
go back to reference Bache M, Kappler M, Said HM et al (2008) Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies. Curr Med Chem 15:322–338PubMedCrossRef Bache M, Kappler M, Said HM et al (2008) Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies. Curr Med Chem 15:322–338PubMedCrossRef
10.
go back to reference Masahi U, Hideo S (2013) Visualization and treatment of the HIF-1-active microenvironments in tumors: drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments. In: Vordermark D (ed) Hypoxia: causes, types and management, 1st edn. Nova Publishers, New York, pp 221–235 Masahi U, Hideo S (2013) Visualization and treatment of the HIF-1-active microenvironments in tumors: drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments. In: Vordermark D (ed) Hypoxia: causes, types and management, 1st edn. Nova Publishers, New York, pp 221–235
11.
go back to reference Schilling D, Bayer C, Emmerich K et al (2012) Basal HIF-1α expression levels are not predictive of radiosensitivity of human cancer cell lines. Strahlenther Onkol 188:353–358PubMedCrossRef Schilling D, Bayer C, Emmerich K et al (2012) Basal HIF-1α expression levels are not predictive of radiosensitivity of human cancer cell lines. Strahlenther Onkol 188:353–358PubMedCrossRef
12.
go back to reference Le QT, Kong C, Lavori PW et al (2007) Expression and prognostic significance of a panel of tissue hypoxia markers in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 69:167–175PubMedCrossRef Le QT, Kong C, Lavori PW et al (2007) Expression and prognostic significance of a panel of tissue hypoxia markers in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 69:167–175PubMedCrossRef
13.
go back to reference Kim SJ, Rabbani ZN, Dewhirst MW et al (2005) Expression of HIF-1α, CA-IX, VEGF and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325–335PubMedCrossRef Kim SJ, Rabbani ZN, Dewhirst MW et al (2005) Expression of HIF-1α, CA-IX, VEGF and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325–335PubMedCrossRef
14.
go back to reference Ilie M, Mazure NM, Hofman V et al (2010) High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J Cancer 25:1627–1635CrossRef Ilie M, Mazure NM, Hofman V et al (2010) High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J Cancer 25:1627–1635CrossRef
15.
go back to reference Hoogsteen IJ, Marres HA, Bussink J et al (2007) Tumor microenvironment in head and neck squamous cell carcinoma: predictive value and clinical relevance of hypoxic markers. A review. Head Neck 29:591–604PubMedCrossRef Hoogsteen IJ, Marres HA, Bussink J et al (2007) Tumor microenvironment in head and neck squamous cell carcinoma: predictive value and clinical relevance of hypoxic markers. A review. Head Neck 29:591–604PubMedCrossRef
16.
go back to reference Zhu Y, Denhardt DT, Cao H et al (2005) Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer. Oncogene 24:6555–6563PubMed Zhu Y, Denhardt DT, Cao H et al (2005) Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer. Oncogene 24:6555–6563PubMed
17.
go back to reference Le QT, Chen E, Salim A et al (2006) An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res 12:1507–1514PubMedCrossRef Le QT, Chen E, Salim A et al (2006) An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res 12:1507–1514PubMedCrossRef
18.
go back to reference Overgaard J, Eriksen JG, Nordsmark M et al (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol 6:757–764PubMedCrossRef Overgaard J, Eriksen JG, Nordsmark M et al (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol 6:757–764PubMedCrossRef
19.
go back to reference Mack PC, Redman MW, Chansky K et al (2008) SWOG: Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol 26:4771–4776PubMedCentralPubMedCrossRef Mack PC, Redman MW, Chansky K et al (2008) SWOG: Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol 26:4771–4776PubMedCentralPubMedCrossRef
20.
go back to reference Blasberg JD, Pass HI, Goparaju CM et al (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28:936–941PubMedCentralPubMedCrossRef Blasberg JD, Pass HI, Goparaju CM et al (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28:936–941PubMedCentralPubMedCrossRef
21.
go back to reference Raja R, Kale S, Thorat D et al (2013) Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF-1α-mediated VEGF-dependent angiogenesis. Oncogene doi:10.1038/onc.2013.171 Raja R, Kale S, Thorat D et al (2013) Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF-1α-mediated VEGF-dependent angiogenesis. Oncogene doi:10.1038/onc.2013.171
22.
go back to reference Senger DR, Ledbetter SR, Claffey KP et al (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the av b 3 integrin osteopontin, and thrombin. Am J Pathol 149:293–305PubMedCentralPubMed Senger DR, Ledbetter SR, Claffey KP et al (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the av b 3 integrin osteopontin, and thrombin. Am J Pathol 149:293–305PubMedCentralPubMed
23.
go back to reference Solberg TD, Nearman J, Mullins J et al (2008) Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy. Int J Radiat Oncol Biol Phys 72:918–926PubMedCentralPubMedCrossRef Solberg TD, Nearman J, Mullins J et al (2008) Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy. Int J Radiat Oncol Biol Phys 72:918–926PubMedCentralPubMedCrossRef
24.
go back to reference Zhao X, Liu X, Guo W et al (2010) Expression of carbonic anhydrase IX in NSCLC and its relationship with VEGF and Ki67 expression. Chin J Cancer 13:881–866 Zhao X, Liu X, Guo W et al (2010) Expression of carbonic anhydrase IX in NSCLC and its relationship with VEGF and Ki67 expression. Chin J Cancer 13:881–866
25.
go back to reference Beasley NJ, Wykoff CC, Watson PH et al (2001) Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. Cancer Res 61:5262–5267PubMed Beasley NJ, Wykoff CC, Watson PH et al (2001) Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. Cancer Res 61:5262–5267PubMed
26.
go back to reference Le QT, Sutphin PD, Raychaudhuri S et al (2003) Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res 9:59–67PubMed Le QT, Sutphin PD, Raychaudhuri S et al (2003) Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res 9:59–67PubMed
27.
go back to reference Snitcovsky I, Leitão GM, Pasini FS et al (2009) Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. Arch Otolaryngol Head Neck Surg 135:807–811PubMedCrossRef Snitcovsky I, Leitão GM, Pasini FS et al (2009) Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. Arch Otolaryngol Head Neck Surg 135:807–811PubMedCrossRef
28.
go back to reference Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549PubMedCentralPubMedCrossRef Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549PubMedCentralPubMedCrossRef
29.
go back to reference Helbig L, Yaromina A, Sriramareddy SN et al (2012) Prognostic value of HIF-1α expression during fractionated irradiation. Strahlenther Onkol 188:1031–1037PubMedCrossRef Helbig L, Yaromina A, Sriramareddy SN et al (2012) Prognostic value of HIF-1α expression during fractionated irradiation. Strahlenther Onkol 188:1031–1037PubMedCrossRef
30.
go back to reference Dellas K, Bache M, Pigorsch SU (2008) Prognostic impact of HIF-1alpha expression in patients with definitive radiotherapy for cervival cancer. Strahlenther Onkol 284:169–174CrossRef Dellas K, Bache M, Pigorsch SU (2008) Prognostic impact of HIF-1alpha expression in patients with definitive radiotherapy for cervival cancer. Strahlenther Onkol 284:169–174CrossRef
31.
go back to reference Bache M, Reddemann R, Said HM et al (2006) Immunohistochemical detection of osteopontin in advanced head and neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1-alpha-related markers, and hemoglobin levels. Int J Radiat Oncol Biol Phys 66:1481–1487PubMedCrossRef Bache M, Reddemann R, Said HM et al (2006) Immunohistochemical detection of osteopontin in advanced head and neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1-alpha-related markers, and hemoglobin levels. Int J Radiat Oncol Biol Phys 66:1481–1487PubMedCrossRef
32.
go back to reference Dunst J, Becker A, Lautenschläger C (2002) Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF). Strahlenther Onkol 178:436–441PubMedCrossRef Dunst J, Becker A, Lautenschläger C (2002) Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF). Strahlenther Onkol 178:436–441PubMedCrossRef
33.
go back to reference Dunst J, Stadler P, Becker A et al (2001) Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers. Strahlenther Onkol 177:469–473PubMedCrossRef Dunst J, Stadler P, Becker A et al (2001) Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers. Strahlenther Onkol 177:469–473PubMedCrossRef
34.
go back to reference Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 18:243–259PubMedCrossRef Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 18:243–259PubMedCrossRef
35.
go back to reference Chang YS, Kim HJ, Chang J (2007) Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer. Lung Cancer 57:373–380PubMedCrossRef Chang YS, Kim HJ, Chang J (2007) Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer. Lung Cancer 57:373–380PubMedCrossRef
36.
go back to reference Karadag F, Gulen ST, Karul AB et al (2011) Osteopontin as a marker of weight loss in lung cancer. Scand J Clin Lab Invest 71:690–694PubMedCrossRef Karadag F, Gulen ST, Karul AB et al (2011) Osteopontin as a marker of weight loss in lung cancer. Scand J Clin Lab Invest 71:690–694PubMedCrossRef
37.
go back to reference Bache M, Kappler M, Wichman H et al (2010) Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients. BMC Cancer 10:132–140PubMedCentralPubMedCrossRef Bache M, Kappler M, Wichman H et al (2010) Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients. BMC Cancer 10:132–140PubMedCentralPubMedCrossRef
38.
go back to reference Soliman M, Yaromina A, Appold S et al (2013) GTV differentially impacts locoregional control of non small-cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWELL trial. Radiother Oncol 106:299–304PubMedCrossRef Soliman M, Yaromina A, Appold S et al (2013) GTV differentially impacts locoregional control of non small-cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWELL trial. Radiother Oncol 106:299–304PubMedCrossRef
39.
go back to reference Ball DL, Fisher RJ, Burmeister BH et al (2013) The complex relationship between lung tumor volume and survival in patients with non small-cell lung cancer treated by definite radiotherapy: a prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305–311PubMedCrossRef Ball DL, Fisher RJ, Burmeister BH et al (2013) The complex relationship between lung tumor volume and survival in patients with non small-cell lung cancer treated by definite radiotherapy: a prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305–311PubMedCrossRef
40.
go back to reference Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143–158PubMedCrossRef Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143–158PubMedCrossRef
41.
go back to reference Takenaka M, Hanagiri T, Shinohara S et al (2012) Serum level of osteopontin as a prognostic factor in patients who underwent surgical resection for non-small cell lung cancer. Clin Lung Cancer 31:S1525–S7304 Takenaka M, Hanagiri T, Shinohara S et al (2012) Serum level of osteopontin as a prognostic factor in patients who underwent surgical resection for non-small cell lung cancer. Clin Lung Cancer 31:S1525–S7304
43.
go back to reference Mayer A, Höckel M, Vaupel P (2008) Endogenous hypoxia markers: case not proven! Adv Exp Med Biol 614:127–136PubMedCrossRef Mayer A, Höckel M, Vaupel P (2008) Endogenous hypoxia markers: case not proven! Adv Exp Med Biol 614:127–136PubMedCrossRef
44.
go back to reference Weber GF (2011) The cancer biomarker osteopontin: combination with other markers. Cancer Genomics Proteomics 8:263–288PubMed Weber GF (2011) The cancer biomarker osteopontin: combination with other markers. Cancer Genomics Proteomics 8:263–288PubMed
45.
go back to reference De Schutter H, Landuyt W, Verbeken E et al (2005) The prognostic value of the hypoxia markers CA IX and GLUT I and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy. BMC Cancer 5:42–53CrossRef De Schutter H, Landuyt W, Verbeken E et al (2005) The prognostic value of the hypoxia markers CA IX and GLUT I and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy. BMC Cancer 5:42–53CrossRef
46.
go back to reference Byers LA, Holsinger FC, Kies MS et al (2010) Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer. Mol Cancer Ther 9:1755–1763PubMedCentralPubMedCrossRef Byers LA, Holsinger FC, Kies MS et al (2010) Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer. Mol Cancer Ther 9:1755–1763PubMedCentralPubMedCrossRef
47.
go back to reference Yaromina A, Quennet V, Zips D et al (2009) Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human suqmous cell carcinoma (hSCC) xenografts. Int J Radiat Biol 85:971–980CrossRef Yaromina A, Quennet V, Zips D et al (2009) Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human suqmous cell carcinoma (hSCC) xenografts. Int J Radiat Biol 85:971–980CrossRef
48.
go back to reference Zips D, Zöphel K, Abolmaali N et al (2012) Exploratory prospective trial of hypoxia-specific PET-imaging during radiochemotherapy in patients with locally advanced head-and-neack cancer. Radiother Oncol 105:21–28PubMedCrossRef Zips D, Zöphel K, Abolmaali N et al (2012) Exploratory prospective trial of hypoxia-specific PET-imaging during radiochemotherapy in patients with locally advanced head-and-neack cancer. Radiother Oncol 105:21–28PubMedCrossRef
49.
go back to reference Mönnich D, Troost EG, Kaanders JH et al (2013) Correlation between tumor oxygenation and (18)F-fluoromisonidazole PET data simulated based on microvessel images. Acta Oncol 52:1308–1313PubMedCrossRef Mönnich D, Troost EG, Kaanders JH et al (2013) Correlation between tumor oxygenation and (18)F-fluoromisonidazole PET data simulated based on microvessel images. Acta Oncol 52:1308–1313PubMedCrossRef
50.
go back to reference Erpolat, Gocun PO, Akmansu M et al (2013) Hypoxia-related molecules HIF-1α, CA9, and osteopontin. Predictors of survival in patients with high-grade glioma. Strahlenther Onkol 189:147–154PubMedCrossRef Erpolat, Gocun PO, Akmansu M et al (2013) Hypoxia-related molecules HIF-1α, CA9, and osteopontin. Predictors of survival in patients with high-grade glioma. Strahlenther Onkol 189:147–154PubMedCrossRef
51.
go back to reference Dehing-Oberije C, Aerts H, Yu S et al (2011) Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys 81:360–368PubMedCrossRef Dehing-Oberije C, Aerts H, Yu S et al (2011) Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys 81:360–368PubMedCrossRef
52.
go back to reference Staab A, Fleischer M, Loeffler J et al (2011) Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro. Strahlenther Onkol 187:252–259PubMedCrossRef Staab A, Fleischer M, Loeffler J et al (2011) Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro. Strahlenther Onkol 187:252–259PubMedCrossRef
53.
go back to reference Vordermark D (2010) Hypoxia-specific targets in cancer therapy: role of splice variants. BMC Med 12:1741–7015 Vordermark D (2010) Hypoxia-specific targets in cancer therapy: role of splice variants. BMC Med 12:1741–7015
Metadata
Title
A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer
Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor
Authors
C. Ostheimer
M. Bache
A. Güttler
M. Kotzsch
D. Vordermark
Publication date
01-03-2014
Publisher
Springer-Verlag
Published in
Strahlentherapie und Onkologie / Issue 3/2014
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-013-0484-1

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