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Erschienen in: Annals of Nuclear Medicine 2/2019

01.02.2019 | Original Article

18F-fluorodeoxyglucose positron emission tomography is correlated with the pathological necrosis and decreased microvessel density in lung adenocarcinomas

verfasst von: Young Wha Koh, Su Jin Lee, Seong Yong Park

Erschienen in: Annals of Nuclear Medicine | Ausgabe 2/2019

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Abstract

Objective

We explored the relationship between preoperative 18F-FDG-PET parameters, tumor necrosis, and microvessel density (MVD) in patients with pulmonary adenocarcinomas.

Methods

A total of 164 patients, who underwent surgical resection for lung adenocarcinoma, were reviewed retrospectively. The maximum standardized uptake value (SUVmax), peak SUV corrected for lean body mass (SULpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values were measured by preoperative 18F-FDG-PET. The extent of tumor necrosis was examined and CD31 expression was evaluated to count the MVD.

Results

The SUVmax, SULpeak, MTV, and TLG levels were significantly lower in patients exhibiting no necrosis compared to those with necrosis. When we divided the patients into two groups based on high vs. low PET parameter values, elevated SUVmax, SULpeak, MTV, and TLG values were significantly more associated with partial or diffuse necrosis than were lower values (p < 0.001). A negative correlation was evident between the MVD and SUVmax, MVD and SULpeak, MVD and MTV, and MVD and TLG. Tumor necrosis was correlated with a shorter overall survival (OS) (p = 0.007) and recur-free survival (RFS) (p < 0.001). However, multivariate analysis revealed that necrosis was not of prognostic significance. The SUVmax, MTV and TLG were associated with inferior OS or RFS rates in univariate analysis, however, not in multivariate analysis.

Conclusion

High-level FDG accumulation is correlated with tumor necrosis in lung adenocarcinoma.
Literatur
1.
Zurück zum Zitat Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26:225–39.CrossRefPubMed Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26:225–39.CrossRefPubMed
2.
Zurück zum Zitat Park SY, Lee HS, Jang HJ, Lee GK, Chung KY, Zo JI. Tumor necrosis as a prognostic factor for stage IA non-small cell lung cancer. Ann Thorac Surg. 2011;91:1668–73.CrossRefPubMed Park SY, Lee HS, Jang HJ, Lee GK, Chung KY, Zo JI. Tumor necrosis as a prognostic factor for stage IA non-small cell lung cancer. Ann Thorac Surg. 2011;91:1668–73.CrossRefPubMed
3.
Zurück zum Zitat Shahab I, Fraire AE, Greenberg SD, Johnson EH, Langston C, Roggli VL. Morphometric quantitation of tumor necrosis in stage 1 non-small cell carcinoma of lung: prognostic implications. Mod Pathol. 1992;5:521–4.PubMed Shahab I, Fraire AE, Greenberg SD, Johnson EH, Langston C, Roggli VL. Morphometric quantitation of tumor necrosis in stage 1 non-small cell carcinoma of lung: prognostic implications. Mod Pathol. 1992;5:521–4.PubMed
4.
Zurück zum Zitat Berghoff AS, Ilhan-Mutlu A, Wohrer A, Hackl M, Widhalm G, Hainfellner JA, et al. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases. Strahlenther Onkol. 2014;190:676–85.CrossRefPubMed Berghoff AS, Ilhan-Mutlu A, Wohrer A, Hackl M, Widhalm G, Hainfellner JA, et al. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases. Strahlenther Onkol. 2014;190:676–85.CrossRefPubMed
5.
Zurück zum Zitat Giatromanolaki A, Koukourakis M, O’Byrne K, Fox S, Whitehouse R, Talbot DC, et al. Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol. 1996;179:80–8.CrossRefPubMed Giatromanolaki A, Koukourakis M, O’Byrne K, Fox S, Whitehouse R, Talbot DC, et al. Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol. 1996;179:80–8.CrossRefPubMed
6.
Zurück zum Zitat Burger IA, Casanova R, Steiger S, Husmann L, Stolzmann P, Huellner MW, et al. 18F-FDG PET/CT of non-small cell lung carcinoma under neoadjuvant chemotherapy: background-based adaptive-volume metrics outperform TLG and MTV in predicting histopathologic response. J Nucl Med. 2016;57:849–54.CrossRefPubMedPubMedCentral Burger IA, Casanova R, Steiger S, Husmann L, Stolzmann P, Huellner MW, et al. 18F-FDG PET/CT of non-small cell lung carcinoma under neoadjuvant chemotherapy: background-based adaptive-volume metrics outperform TLG and MTV in predicting histopathologic response. J Nucl Med. 2016;57:849–54.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Dooms C, van Baardwijk A, Verbeken E, van Suylen RJ, Stroobants S, De Ruysscher D, et al. Association between 18F-fluoro-2-deoxy-d-glucose uptake values and tumor vitality: prognostic value of positron emission tomography in early-stage non-small cell lung cancer. J Thorac Oncol. 2009;4:822–8.CrossRefPubMed Dooms C, van Baardwijk A, Verbeken E, van Suylen RJ, Stroobants S, De Ruysscher D, et al. Association between 18F-fluoro-2-deoxy-d-glucose uptake values and tumor vitality: prognostic value of positron emission tomography in early-stage non-small cell lung cancer. J Thorac Oncol. 2009;4:822–8.CrossRefPubMed
8.
Zurück zum Zitat Vesselle H, Salskov A, Turcotte E, Wiens L, Schmidt R, Jordan CD, et al. Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol. 2008;3:971–8.CrossRefPubMed Vesselle H, Salskov A, Turcotte E, Wiens L, Schmidt R, Jordan CD, et al. Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol. 2008;3:971–8.CrossRefPubMed
9.
Zurück zum Zitat Semenza GL, editor. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Seminars in cancer biology. Amsterdam: Elsevier; 2009. Semenza GL, editor. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Seminars in cancer biology. Amsterdam: Elsevier; 2009.
10.
Zurück zum Zitat Shan X, Wang D, Chen J, Xiao X, Jiang Y, Wang Y, et al. Necrosis degree displayed in computed tomography images correlated with hypoxia and angiogenesis in breast cancer. J Comput Assist Tomogr. 2013;37:22–8.CrossRefPubMed Shan X, Wang D, Chen J, Xiao X, Jiang Y, Wang Y, et al. Necrosis degree displayed in computed tomography images correlated with hypoxia and angiogenesis in breast cancer. J Comput Assist Tomogr. 2013;37:22–8.CrossRefPubMed
11.
Zurück zum Zitat Schuurbiers OC, Meijer TW, Kaanders JH, Looijen-Salamon MG, de Geus-Oei LF, van der Drift MA, et al. Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma. J Thorac Oncol. 2014;9:1485–93.CrossRefPubMed Schuurbiers OC, Meijer TW, Kaanders JH, Looijen-Salamon MG, de Geus-Oei LF, van der Drift MA, et al. Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma. J Thorac Oncol. 2014;9:1485–93.CrossRefPubMed
12.
Zurück zum Zitat Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, et al. Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor. PLoS One. 2014;9:e86459.CrossRefPubMedPubMedCentral Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, et al. Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor. PLoS One. 2014;9:e86459.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Fang YH, Lin CY, Shih MJ, Wang HM, Ho TY, Liao CT, et al. Development and evaluation of an open-source software package “CGITA” for quantifying tumor heterogeneity with molecular images. Biomed Res Int. 2014;2014:248505.PubMedPubMedCentral Fang YH, Lin CY, Shih MJ, Wang HM, Ho TY, Liao CT, et al. Development and evaluation of an open-source software package “CGITA” for quantifying tumor heterogeneity with molecular images. Biomed Res Int. 2014;2014:248505.PubMedPubMedCentral
14.
Zurück zum Zitat Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. The 2015 World Health Organization Classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10:1243–60.CrossRefPubMed Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, et al. The 2015 World Health Organization Classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10:1243–60.CrossRefPubMed
15.
Zurück zum Zitat Jeong D, Ban S, Oh S, Jin Lee S, Yong Park S, Koh YW. Prognostic significance of EDIL3 expression and correlation with mesenchymal phenotype and microvessel density in lung adenocarcinoma. Sci Rep. 2017;7:8649.CrossRefPubMedPubMedCentral Jeong D, Ban S, Oh S, Jin Lee S, Yong Park S, Koh YW. Prognostic significance of EDIL3 expression and correlation with mesenchymal phenotype and microvessel density in lung adenocarcinoma. Sci Rep. 2017;7:8649.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Pollheimer MJ, Kornprat P, Lindtner RA, Harbaum L, Schlemmer A, Rehak P, et al. Tumor necrosis is a new promising prognostic factor in colorectal cancer. Hum Pathol. 2010;41:1749–57.CrossRefPubMed Pollheimer MJ, Kornprat P, Lindtner RA, Harbaum L, Schlemmer A, Rehak P, et al. Tumor necrosis is a new promising prognostic factor in colorectal cancer. Hum Pathol. 2010;41:1749–57.CrossRefPubMed
18.
Zurück zum Zitat Hirsch FR, Spreafico A, Novello S, Wood MD, Simms L, Papotti M. The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol. 2008;3:1468–81.CrossRefPubMed Hirsch FR, Spreafico A, Novello S, Wood MD, Simms L, Papotti M. The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol. 2008;3:1468–81.CrossRefPubMed
19.
Zurück zum Zitat Caruso R, Parisi A, Bonanno A, Paparo D, Quattrocchi E, Branca G, et al. Histologic coagulative tumour necrosis as a prognostic indicator of aggressiveness in renal, lung, thyroid and colorectal carcinomas: a brief review. Oncol Lett. 2012;3:16–8.CrossRefPubMed Caruso R, Parisi A, Bonanno A, Paparo D, Quattrocchi E, Branca G, et al. Histologic coagulative tumour necrosis as a prognostic indicator of aggressiveness in renal, lung, thyroid and colorectal carcinomas: a brief review. Oncol Lett. 2012;3:16–8.CrossRefPubMed
20.
Zurück zum Zitat Adams HJA, de Klerk JMH, Fijnheer R, Heggelman BGF, Dubois SV, Nievelstein RAJ, et al. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma. Eur J Radiol. 2016;85:304–9.CrossRefPubMed Adams HJA, de Klerk JMH, Fijnheer R, Heggelman BGF, Dubois SV, Nievelstein RAJ, et al. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma. Eur J Radiol. 2016;85:304–9.CrossRefPubMed
21.
Zurück zum Zitat Rakheja R, Makis W, Tulbah R, Skamene S, Holcroft C, Nahal A, et al. Necrosis on FDG PET/CT correlates with prognosis and mortality in sarcomas. AJR Am J Roentgenol. 2013;201:170–7.CrossRefPubMed Rakheja R, Makis W, Tulbah R, Skamene S, Holcroft C, Nahal A, et al. Necrosis on FDG PET/CT correlates with prognosis and mortality in sarcomas. AJR Am J Roentgenol. 2013;201:170–7.CrossRefPubMed
22.
Zurück zum Zitat Foster JG, Wong SC, Sharp TV. The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol. 2014;10:2659–74.CrossRef Foster JG, Wong SC, Sharp TV. The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol. 2014;10:2659–74.CrossRef
23.
Zurück zum Zitat Daster S, Amatruda N, Calabrese D, Ivanek R, Turrini E, Droeser RA, et al. Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment. Oncotarget. 2017;8:1725–36.CrossRefPubMed Daster S, Amatruda N, Calabrese D, Ivanek R, Turrini E, Droeser RA, et al. Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment. Oncotarget. 2017;8:1725–36.CrossRefPubMed
24.
Zurück zum Zitat Chou CW, Wang CC, Wu CP, Lin YJ, Lee YC, Cheng YW, et al. Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1. Neuro Oncol. 2012;14:1227–38.CrossRefPubMedPubMedCentral Chou CW, Wang CC, Wu CP, Lin YJ, Lee YC, Cheng YW, et al. Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1. Neuro Oncol. 2012;14:1227–38.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Sasaki T, Yamamoto M, Yamaguchi T, Sugiyama S. Development of multicellular spheroids of HeLa cells cocultured with fibroblasts and their response to X-irradiation. Cancer Res. 1984;44:345–51.PubMed Sasaki T, Yamamoto M, Yamaguchi T, Sugiyama S. Development of multicellular spheroids of HeLa cells cocultured with fibroblasts and their response to X-irradiation. Cancer Res. 1984;44:345–51.PubMed
26.
Zurück zum Zitat Minakata K, Takahashi F, Nara T, Hashimoto M, Tajima K, Murakami A, et al. Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors. Cancer Sci. 2012;103:1946–54.CrossRefPubMed Minakata K, Takahashi F, Nara T, Hashimoto M, Tajima K, Murakami A, et al. Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors. Cancer Sci. 2012;103:1946–54.CrossRefPubMed
27.
Zurück zum Zitat Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond). 2012;7:597–615.CrossRef Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond). 2012;7:597–615.CrossRef
28.
Zurück zum Zitat Park SY, Cho A, Yu WS, Lee CY, Lee JG, Kim DJ, et al. Prognostic value of total lesion glycolysis by 18F-FDG PET/CT in surgically resected stage IA non-small cell lung cancer. J Nucl Med. 2015;56:45–9.CrossRefPubMed Park SY, Cho A, Yu WS, Lee CY, Lee JG, Kim DJ, et al. Prognostic value of total lesion glycolysis by 18F-FDG PET/CT in surgically resected stage IA non-small cell lung cancer. J Nucl Med. 2015;56:45–9.CrossRefPubMed
29.
Zurück zum Zitat Hyun SH, Ahn HK, Kim H, Ahn MJ, Park K, Ahn YC, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41:50–8.CrossRefPubMed Hyun SH, Ahn HK, Kim H, Ahn MJ, Park K, Ahn YC, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41:50–8.CrossRefPubMed
30.
Zurück zum Zitat Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38.CrossRefPubMed Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38.CrossRefPubMed
Metadaten
Titel
18F-fluorodeoxyglucose positron emission tomography is correlated with the pathological necrosis and decreased microvessel density in lung adenocarcinomas
verfasst von
Young Wha Koh
Su Jin Lee
Seong Yong Park
Publikationsdatum
01.02.2019
Verlag
Springer Singapore
Erschienen in
Annals of Nuclear Medicine / Ausgabe 2/2019
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-018-1309-1

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