Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 4/2018

21.06.2017 | Original Research

Venous Thromboembolism Is an Independent Predictor of Mortality Among Patients with Gastric Cancer

verfasst von: Harry E. Fuentes, D. M. Oramas, L. H. Paz, Y. Wang, X. A. Andrade, A. J. Tafur

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Venous thromboembolism (VTE) is an independent predictor of death among patients with cancer. Patients with gastric cancer (GC) are at higher risk for VTE when compared to other solid tumors, and if one considers its prevalence, GC may be responsible for one of the highest incidences of cancer-associated thrombosis. The impact of VTE on mortality is not well defined among patients with GC.

Aim

The aim of this study is to measure the impact of VTE as independent predictor of GC mortality.

Methods

Chart review of patients with GC treated in the Department of Oncology at John Stroger Hospital between the years of 2010 and 2015. VTE events were objectively confirmed with imaging in all cases. Active GC was defined as biopsy-proven metastatic disease or on active chemotherapy. Along with cancer-specific data, we abstracted risk assessments tools, non-GC-specific, validated for VTE and mortality prediction cancer, including the Khorana score (KRS), platelet lymphocyte ratio (PLR), and neutrophil lymphocyte ratio (NLR). Continuous variables are expressed by the median as appropriate according to normality. Categorical variables are expressed as percentages. SPSS version 22 was used and chi-square, Mann-Whitney U, Kaplan-Meier curve, and Cox proportional hazard with forward modeling were applied.

Results

We included 112 patients in the analysis. The patients were predominantly men (66%), 58-year-old, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (IQR 8.9–42.4). Cumulative incidence of VTE at 1 year was 9%. The median time from diagnosis to VTE occurrence was 59 days (IQR 36 to 258). Patients with VTE had worse OS when compared to the non-VTE group (medians 11.87 vs 29.97 months, p = 0.02). Patients stratified as high risk by the PLR had worse OS (medians 22.6 vs 42.77 months, p = 0.02). There was no statistical difference in OS among patients stratified as high risk by the KRS (medians 23.7 vs 42.5, p = 0.16) and NLR (medians 24.1 vs 42.7 months, p = 0.21). In multivariate analysis, the independent predictors of mortality were VTE (hazard ratio (HR), 2.9; 95% CI, 1.4 to 6.6; p < 0.01), adenocarcinoma (HR, 3.1; 95% CI, 1.1 to 9.0; p = 0.03), advanced disease (HR, 2.8; 95% CI, 1.4 to 5.8; p < 0.01), and PLR (HR, 2.2; 95% CI, 1.3 to 3.8; p < 0.01).

Conclusion

VTE is associated with worse survival among patients with GC along with adenocarcinoma, advanced disease, and PLR. Moreover, these findings were independent of other cancer- and treatment-specific variables. Although potentially predictive in other cancer types, NLR and KRS were not associated with worse survival in this cohort.
Literatur
1.
Zurück zum Zitat Anderson LA, Moore SC, Gridley G, Stone BJ, Landgren O. Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans. Leuk Lymphoma. 2011;52(5):764–70.CrossRef Anderson LA, Moore SC, Gridley G, Stone BJ, Landgren O. Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans. Leuk Lymphoma. 2011;52(5):764–70.CrossRef
2.
Zurück zum Zitat Chen W, Zhang Y, Yang Y, Zhai Z, Wang C. Prognostic significance of arterial and venous thrombosis in resected specimens for non-small cell lung cancer. Thromb Res. 136(2):451–5.CrossRef Chen W, Zhang Y, Yang Y, Zhai Z, Wang C. Prognostic significance of arterial and venous thrombosis in resected specimens for non-small cell lung cancer. Thromb Res. 136(2):451–5.CrossRef
3.
Zurück zum Zitat Diaz ES, Walts AE, Karlan BY, Walsh CS. Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival. Gynecol Oncol. 131(3):541–5.CrossRef Diaz ES, Walts AE, Karlan BY, Walsh CS. Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival. Gynecol Oncol. 131(3):541–5.CrossRef
4.
Zurück zum Zitat Hicks LK, Cheung MC, Ding K, Hasan B, Seymour L, Le Maître A, et al. Venous thromboembolism and nonsmall cell lung cancer. Cancer. 2009;115(23):5516–25.CrossRef Hicks LK, Cheung MC, Ding K, Hasan B, Seymour L, Le Maître A, et al. Venous thromboembolism and nonsmall cell lung cancer. Cancer. 2009;115(23):5516–25.CrossRef
5.
Zurück zum Zitat Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–4.CrossRef Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–4.CrossRef
6.
Zurück zum Zitat Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.CrossRef Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.CrossRef
7.
Zurück zum Zitat Cronin-Fenton DP, Sondergaard F, Pedersen LA, Fryzek JP, Cetin K, Acquavella J, et al. Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997–2006. Br J Cancer. 2010;103(7):947–53.CrossRef Cronin-Fenton DP, Sondergaard F, Pedersen LA, Fryzek JP, Cetin K, Acquavella J, et al. Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997–2006. Br J Cancer. 2010;103(7):947–53.CrossRef
8.
Zurück zum Zitat Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ III. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809–15.CrossRef Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ III. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000;160(6):809–15.CrossRef
9.
Zurück zum Zitat Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer—a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49(6):1404–13.CrossRef Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer—a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49(6):1404–13.CrossRef
10.
Zurück zum Zitat Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer. 2011;117(7):1334–49.CrossRef Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer. 2011;117(7):1334–49.CrossRef
11.
Zurück zum Zitat Lyman GH. The incidence of venous thromboembolism in cancer patients: a real-world analysis. Clin Adv Hematol Oncol. 2012;10(1):40–2.PubMed Lyman GH. The incidence of venous thromboembolism in cancer patients: a real-world analysis. Clin Adv Hematol Oncol. 2012;10(1):40–2.PubMed
12.
Zurück zum Zitat Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore). 1999;78(5):285–91.CrossRef Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore). 1999;78(5):285–91.CrossRef
13.
Zurück zum Zitat Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.CrossRef Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.CrossRef
14.
Zurück zum Zitat Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006;119(1):60–8.CrossRef Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006;119(1):60–8.CrossRef
15.
Zurück zum Zitat De Cicco M. The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol. 2004;50(3):187–96.CrossRef De Cicco M. The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol. 2004;50(3):187–96.CrossRef
16.
Zurück zum Zitat Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166(4):458–64.CrossRef Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166(4):458–64.CrossRef
17.
Zurück zum Zitat Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343(25):1846–50.CrossRef Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343(25):1846–50.CrossRef
18.
Zurück zum Zitat Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol. 2006;24(7):1112–8.CrossRef Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol. 2006;24(7):1112–8.CrossRef
19.
Zurück zum Zitat Mandala M, Barni S, Floriani I, Isa L, Fornarini G, Marangolo M, et al. Incidence and clinical implications of venous thromboembolism in advanced colorectal cancer patients: the ‘GISCAD-alternating schedule’ study findings. Eur J Cancer. 2009;45(1):65–73.CrossRef Mandala M, Barni S, Floriani I, Isa L, Fornarini G, Marangolo M, et al. Incidence and clinical implications of venous thromboembolism in advanced colorectal cancer patients: the ‘GISCAD-alternating schedule’ study findings. Eur J Cancer. 2009;45(1):65–73.CrossRef
20.
Zurück zum Zitat Mandala M, Reni M, Cascinu S, Barni S, Floriani I, Cereda S, et al. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Ann Oncol. 2007;18(10):1660–5.CrossRef Mandala M, Reni M, Cascinu S, Barni S, Floriani I, Cereda S, et al. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Ann Oncol. 2007;18(10):1660–5.CrossRef
21.
Zurück zum Zitat Dempsey LA, Brunn GJ, Platt JL. Heparanase, a potential regulator of cell-matrix interactions. Trends Biochem Sci. 2000;25(8):349–51.CrossRef Dempsey LA, Brunn GJ, Platt JL. Heparanase, a potential regulator of cell-matrix interactions. Trends Biochem Sci. 2000;25(8):349–51.CrossRef
22.
Zurück zum Zitat Parish CR, Freeman C, Hulett MD. Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta. 2001;1471(3):M99–108.PubMed Parish CR, Freeman C, Hulett MD. Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta. 2001;1471(3):M99–108.PubMed
23.
Zurück zum Zitat Vlodavsky I, Friedmann Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest. 2001;108(3):341–7.CrossRef Vlodavsky I, Friedmann Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest. 2001;108(3):341–7.CrossRef
24.
Zurück zum Zitat Aliustaoglu M, Bilici A, Seker M, Dane F, Gocun M, Konya V, et al. The association of pre-treatment peripheral blood markers with survival in patients with pancreatic cancer. Hepato-Gastroenterology. 2010;57(99–100):640–5.PubMed Aliustaoglu M, Bilici A, Seker M, Dane F, Gocun M, Konya V, et al. The association of pre-treatment peripheral blood markers with survival in patients with pancreatic cancer. Hepato-Gastroenterology. 2010;57(99–100):640–5.PubMed
25.
Zurück zum Zitat He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013;30(1):439.CrossRef He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013;30(1):439.CrossRef
26.
Zurück zum Zitat Jin H, Zhang G, Liu X, Liu X, Chen C, Yu H, et al. Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol. 2013;11:112.CrossRef Jin H, Zhang G, Liu X, Liu X, Chen C, Yu H, et al. Blood neutrophil-lymphocyte ratio predicts survival for stages III-IV gastric cancer treated with neoadjuvant chemotherapy. World J Surg Oncol. 2013;11:112.CrossRef
27.
Zurück zum Zitat Luo G, Guo M, Liu Z, Xiao Z, Jin K, Long J, et al. Blood neutrophil-lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy. Ann Surg Oncol. 2015;22(2):670–6.CrossRef Luo G, Guo M, Liu Z, Xiao Z, Jin K, Long J, et al. Blood neutrophil-lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy. Ann Surg Oncol. 2015;22(2):670–6.CrossRef
28.
Zurück zum Zitat Yang W, Liu Y. Platelet-lymphocyte ratio is a predictor of venous thromboembolism in cancer patients. Thromb Res. 2015;136(2):212–5.CrossRef Yang W, Liu Y. Platelet-lymphocyte ratio is a predictor of venous thromboembolism in cancer patients. Thromb Res. 2015;136(2):212–5.CrossRef
29.
Zurück zum Zitat Yuan D, Zhu K, Li K, Yan R, Jia Y, Dang C. The preoperative neutrophil-lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction. J Surg Oncol. 2014;110(3):333–40.CrossRef Yuan D, Zhu K, Li K, Yan R, Jia Y, Dang C. The preoperative neutrophil-lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction. J Surg Oncol. 2014;110(3):333–40.CrossRef
30.
Zurück zum Zitat Kuderer NM, Culakova E, Lyman GH, Francis C, Falanga A, Khorana AA. A validated risk score for venous thromboembolism is predictive of cancer progression and mortality. Oncologist. 2016;21(7):861–7.CrossRef Kuderer NM, Culakova E, Lyman GH, Francis C, Falanga A, Khorana AA. A validated risk score for venous thromboembolism is predictive of cancer progression and mortality. Oncologist. 2016;21(7):861–7.CrossRef
31.
Zurück zum Zitat Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006;24(33):5201–6.CrossRef Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006;24(33):5201–6.CrossRef
32.
Zurück zum Zitat Tetzlaff ED, Correa AM, Baker J, Ensor J, Ajani JA. The impact on survival of thromboembolic phenomena occurring before and during protocol chemotherapy in patients with advanced gastroesophageal adenocarcinoma. Cancer. 2007;109(10):1989–95.CrossRef Tetzlaff ED, Correa AM, Baker J, Ensor J, Ajani JA. The impact on survival of thromboembolic phenomena occurring before and during protocol chemotherapy in patients with advanced gastroesophageal adenocarcinoma. Cancer. 2007;109(10):1989–95.CrossRef
33.
Zurück zum Zitat Tetzlaff ED, Correa AM, Komaki R, Swisher SG, Maru D, Ross WA, et al. Significance of thromboembolic phenomena occurring before and during chemoradiotherapy for localized carcinoma of the esophagus and gastroesophageal junction. Dis Esophagus. 2008;21(7):575–81.CrossRef Tetzlaff ED, Correa AM, Komaki R, Swisher SG, Maru D, Ross WA, et al. Significance of thromboembolic phenomena occurring before and during chemoradiotherapy for localized carcinoma of the esophagus and gastroesophageal junction. Dis Esophagus. 2008;21(7):575–81.CrossRef
34.
Zurück zum Zitat Ferroni P, Riondino S, Formica V, Cereda V, Tosetto L, La Farina F, et al. Venous thromboembolism risk prediction in ambulatory cancer patients: clinical significance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Int J Cancer. 2015;136(5):1234–40.CrossRef Ferroni P, Riondino S, Formica V, Cereda V, Tosetto L, La Farina F, et al. Venous thromboembolism risk prediction in ambulatory cancer patients: clinical significance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Int J Cancer. 2015;136(5):1234–40.CrossRef
35.
Zurück zum Zitat Go S-I, Lee A, Lee US, Choi HJ, Kang MH, Kang J-H, et al. Clinical significance of the neutrophil–lymphocyte ratio in venous thromboembolism patients with lung cancer. Lung Cancer. 84(1):79–85.CrossRef Go S-I, Lee A, Lee US, Choi HJ, Kang MH, Kang J-H, et al. Clinical significance of the neutrophil–lymphocyte ratio in venous thromboembolism patients with lung cancer. Lung Cancer. 84(1):79–85.CrossRef
36.
Zurück zum Zitat Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.CrossRef Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.CrossRef
37.
Zurück zum Zitat Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24(31):4991–7.CrossRef Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24(31):4991–7.CrossRef
38.
Zurück zum Zitat Fuentes HE, Tafur AJ, Caprini JA. Cancer-associated thrombosis. Dis Mon. 2016;62(5):121–58.CrossRef Fuentes HE, Tafur AJ, Caprini JA. Cancer-associated thrombosis. Dis Mon. 2016;62(5):121–58.CrossRef
39.
Zurück zum Zitat Sierko E, Wojtukiewicz MZ. Platelets and angiogenesis in malignancy. Semin Thromb Hemost. 2004;30(1):95–108.CrossRef Sierko E, Wojtukiewicz MZ. Platelets and angiogenesis in malignancy. Semin Thromb Hemost. 2004;30(1):95–108.CrossRef
40.
Zurück zum Zitat Elting LS, Escalante CP, Cooksley C, Avritscher EB, Kurtin D, Hamblin L, et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med. 2004;164(15):1653–61.CrossRef Elting LS, Escalante CP, Cooksley C, Avritscher EB, Kurtin D, Hamblin L, et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med. 2004;164(15):1653–61.CrossRef
41.
Zurück zum Zitat Fuentes HE, Oramas DM, Paz LH, Casanegra AI, Mansfield AS, Tafur AJ. Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer. Thromb Res. 2017;154:28–34.CrossRef Fuentes HE, Oramas DM, Paz LH, Casanegra AI, Mansfield AS, Tafur AJ. Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer. Thromb Res. 2017;154:28–34.CrossRef
42.
Zurück zum Zitat Marshall-Webb M, Bright T, Price T, Thompson SK, Watson DI. Venous thromboembolism in patients with esophageal or gastric cancer undergoing neoadjuvant chemotherapy. Dis Esophagus. 2017;30(2):1–7.PubMed Marshall-Webb M, Bright T, Price T, Thompson SK, Watson DI. Venous thromboembolism in patients with esophageal or gastric cancer undergoing neoadjuvant chemotherapy. Dis Esophagus. 2017;30(2):1–7.PubMed
Metadaten
Titel
Venous Thromboembolism Is an Independent Predictor of Mortality Among Patients with Gastric Cancer
verfasst von
Harry E. Fuentes
D. M. Oramas
L. H. Paz
Y. Wang
X. A. Andrade
A. J. Tafur
Publikationsdatum
21.06.2017
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 4/2018
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-017-9981-2

Weitere Artikel der Ausgabe 4/2018

Journal of Gastrointestinal Cancer 4/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.