Radikal Radyokemoterapi/Radyoterapi Uygulanan Serviks Karsinomu Olgularında Açlık Kan Şekeri Düzeylerinin Tedavi Sonuçlarına Etkisi

Öz

Başlık: Radikal Radyokemoterapi/Radyoterapi Uygulanan Serviks Karsinomu Olgularında Açlık Kan Şekeri Düzeylerinin Tedavi Sonuçlarına Etkisi

Türkçe Özet

Amaç: Serviks kanseri dünya genelinde kadınlarda en sık görülen dördüncü kanserdir. Kanser olgularında yüksek kan şekeri düzeylerinin düşük sağkalımla ilişkisini gösteren birçok klinik çalışma yayınlanmıştır. Serviks kanserinde de artmış açlık kan şekeri (AKŞ) düzeyleri artmış mortalite ile ilişkili bulunmuştur. Bu çalışmada radikal radyokemoterapi/radyoterapi uygulanan serviks karsinomu olgularında AKŞ düzeylerinin yineleme ve genel sağkalıma (GS) etkisinin araştırılması amaçlanmıştır.

 

Gereç ve Yöntem: 2005-2013 arasında evreIB-IVB serviks karsinomu tanısıyla eşzamanlı radyokemoterapi/radyoterapi uygulanan 150 olgunun verileri geriye dönük olarak analiz edilmiştir. AKŞ değerleri tedavi öncesi, tedavi sırası ve tedavi sonrası olmak üzere 3 ayrı dönemde incelenmiştir <100mg/dl normal-AKŞ, ≥100 ve ˂126mg/dl pre-dyiabetik AKŞ, ≥126mg/dl diyabetik-AKŞ olarak kabul edilmiştir.

 

Sonuçlar: Ortanca takip süresi 64 aydı. 5 yıllık GS %57, hastalıksız sağkalım %46’idi. Üç tedavi dönemindeki AKŞ değerlerinin lokal-bölgesel yineleme, uzak yineleme ve GS tahmin için ROC analizi yapıldığında, 100 mg/dl düzeyinin; uzak yineleme için tedavi öncesi dönemde duyarlılığının % 89, özgüllüğünün % 48 (AUC: 0.69, CI: 0.58-0.80) p:0.003, yine uzak yineleme için tedavi sonrası dönemde duyarlılığının % 86, özgüllüğünün % 43 (AUC: 0.69, CI: 0.57-0.80) p:0.004 ve GS için tedavi sonrası dönemde duyarlılığının % 70, özgüllüğünün % 44 (AUC: 0.61, CI: 0.50-0.72) p:0.039 olduğu tespit edilmiştir. Tedavi sonrası dönemde uzak yineleyen ve ex olan olguların ortanca AKŞ düzeyleri uzak yinelemeyen ve yaşayan olgulara göre anlamlı olarak daha yüksek bulunmuştur.

 

 

Sonuç: Tedavi öncesi ve sonrası dönemde 100 mg/dl üzeri AKŞ düzeyleri tedavi sonuçlarını kötüleştirebilir. Uzak yineleyen ve ex olan olgularda tedavi sonrası dönemde AKŞ seviyeleri yinelemeyen ve sağ olgulara göre daha yüksektir. 

İngilizce Özet (Abstract)

Aim: Cervical cancer is the fourth common cancer in women worldwide. The importance of glucose metabolism in cancer developement and progression has been focus of interest in recent years. Increased blood glucose level has been proven to be related with increased mortality in cervical cancer. The aim of this study, is to evaluate the relation between fasting blood glucose levels(FBG) and treatment outcomes in cervical cancer treated with radical radiochemotherapy/radiotherapy.

 

Material and Methods: The medical records of 150 patients with stage IB-IVB cervical cancer treated with radical radiotherapy/radiotherapy between 2005-2013 were reviewed retrospectively. FBG levels were recorded in pre-treatment, treatment and post-treatment periods and were categorised as normal if FBG is <100mg/dl, as pre-diabetic if FBG is ≥100mg/dl and ˂126mg/dl, as diabetic if FBG is ≥126 mg/dl.

 

Results: Median follow-up was 64 months. 5y OS was 57%, 5y DFS was 46%. ROC analyis for FBG was carried out for 3 different treatment periods to predict DM and OS; for 100mg/dl in pre-treatment period was found to have 89% sensitivity,48% specifity (AUC:0.69, CI:0.58-0.80) p:0.003 for  DM, 100mg/dl in post-treatment period was found to have 86% sensitivity,43% specifity (AUC:0.69,CI:0.57-0.80) p:0.004 for DM,  100mg/dl in post-treatment period was found to have 70% sensitivity,44% specifity (AUC:0.61, CI:0.50-0.72) p:0.039  for OS. Patients with DM and died patients had significantly higher median FBG level in post-treatment period compared to non-relapsing and alive patients,

 

Conclusion: 100 mg/dl FBG levels  in pre and post-treatment period might worsen treatment outcomes. The patients with DM and shorter survival had higher FBG levels in post-treatment period.

Anahtar Kelimeler

• serviks karsinomu; hiperglisemi; tedavi sonuçları

Kaynakça

1. 1. Parkin, D.M., F. Bray, J. Ferlay, and P. Pisani, Global cancer statistics, 2002. CA Cancer J Clin, 2005. 55(2): p. 74-108.
2. 2. Torre, L.A., F. Islami, R.L. Siegel, E.M. Ward, and A. Jemal, Global Cancer in Women: Burden and Trends. Cancer Epidemiol Biomarkers Prev, 2017. 26(4): p. 444-457.
3. 3. National Comprehensive Cancer Network, V., Cervical Cancer. 2017.
4. 4. Satija, A., D. Spiegelman, E. Giovannucci, and F.B. Hu, Type 2 diabetes and risk of cancer. BMJ, 2015. 350: p. g7707.
5. 5. Scappaticcio, L., M.I. Maiorino, G. Bellastella, D. Giugliano, and K. Esposito, Insights into the relationships between diabetes, prediabetes, and cancer. Endocrine, 2017. 56(2): p. 231-239.
6. 6. Zanders, M.M., D. Boll, L.N. van Steenbergen, L.V. van de Poll-Franse, and H.R. Haak, Effect of diabetes on endometrial cancer recurrence and survival. Maturitas, 2013. 74(1): p. 37-43.
7. 7. Bakhru, A., R.J. Buckanovich, and J.J. Griggs, The impact of diabetes on survival in women with ovarian cancer. Gynecol Oncol, 2011. 121(1): p. 106-11.
8. 8. In Choi, J., H.K. Chang, D.W. Lee, K.H. Lee, J.S. Park, and H.N. Lee, Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer? Gynecol Oncol, 2015. 139(2): p. 319-23.

9. 9. Chen, S., M. Tao, L. Zhao, and X. Zhang, The association between diabetes/hyperglycemia and the prognosis of cervical cancer patients: A systematic review and meta-analysis. Medicine (Baltimore), 2017. 96(40): p. e7981.
10. 10. Kapp, D.S., D. Fischer, E. Gutierrez, E.I. Kohorn, and P.E. Schwartz, Pretreatment prognostic factors in carcinoma of the uterine cervix: a multivariable analysis of the effect of age, stage, histology and blood counts on survival. Int J Radiat Oncol Biol Phys, 1983. 9(4): p. 445-55.
11. 11. Jiamset, I. and J. Hanprasertpong, Impact of diabetes mellitus on oncological outcomes after radical hysterectomy for early stage cervical cancer. J Gynecol Oncol, 2016. 27(3): p. e28.
12. 12. Nomelini, R.S., A.S. Neto, K.A. Capuci, B.M. Murta, and E.F. Murta, Relationship between plasma glucose levels and malignant uterine cervical neoplasias. Clin Med Insights Oncol, 2011. 5: p. 77-82.
13. 13. Kirakli, E.K., U. Yilmaz, H. Yilmaz, and B. Komurcuoglu, Fasting Blood Glucose Level in Locally Advanced Non-Small Cell Lung Cancer: a New Prognostic Factor? Horm Cancer, 2018. 9(3): p. 188-196.
14. 14. Lee, Y.Y., C.H. Choi, C.J. Kim, et al., Glucose as a prognostic factor in non-diabetic women with locally advanced cervical cancer (IIB-IVA). Gynecol Oncol, 2010. 116(3): p. 459-63.
15. 15. Ahn, H.K., J.W. Shin, H.Y. Ahn, et al., Metabolic components and recurrence in early-stage cervical cancer. Tumour Biol, 2015. 36(3): p. 2201-7.
16. 16. Barone, B.B., H.C. Yeh, C.F. Snyder, et al., Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA, 2008. 300(23): p. 2754-64.
17. 17. Stocks, T., K. Rapp, T. Bjorge, et al., Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): analysis of six prospective cohorts. PLoS Med, 2009. 6(12): p. e1000201.
18. 18. Yung, M.M., D.W. Chan, V.W. Liu, K.M. Yao, and H.Y. Ngan, Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade. BMC Cancer, 2013. 13: p. 327.
19. 19. Tian, R.H., Y.G. Zhang, Z. Wu, X. Liu, J.W. Yang, and H.L. Ji, Effects of metformin on survival outcomes of lung cancer patients with type 2 diabetes mellitus: a meta-analysis. Clin Transl Oncol, 2016. 18(6): p. 641-9.
20. 20. Ko, E.M., P. Walter, A. Jackson, et al., Metformin is associated with improved survival in endometrial cancer. Gynecol Oncol, 2014. 132(2): p. 438-42.
21. 21. Romero, I.L., A. McCormick, K.A. McEwen, et al., Relationship of type II diabetes and metformin use to ovarian cancer progression, survival, and chemosensitivity. Obstet Gynecol, 2012. 119(1): p. 61-7.
22. 22. Warburg, O., On the origin of cancer cells. Science, 1956. 123(3191): p. 309-14.
23. 23. Dasgupta, A., M. Nomura, R. Shuck, and J. Yustein, Cancer's Achilles' Heel: Apoptosis and Necroptosis to the Rescue. Int J Mol Sci, 2016. 18(1).
24. 24. Kim, J.W. and C.V. Dang, Cancer's molecular sweet tooth and the Warburg effect. Cancer Res, 2006. 66(18): p. 8927-30.
25. 25. Gallagher, E.J. and D. LeRoith, Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci, 2011. 1243: p. 54-68.26. Iwatsuki, M., K. Mimori, T. Yokobori, et al., Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci, 2010. 101(2): p. 293-9.
26. 27. 2. Classification and Diagnosis of Diabetes. Diabetes Care, 2017. 40(Suppl 1): p. S11-S24.
27. 28. Nuttall, F.Q., Body Mass Index: Obesity, BMI, and Health: A Critical Review. Nutr Today, 2015. 50(3): p. 117-128.
28. 29. Morris, M., P.J. Eifel, J. Lu, et al., Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med, 1999. 340(15): p. 1137-43.
29. 30. Kinjyo, Y., Y. Nagai, T. Toita, et al., Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy for locally advanced squamous-cell carcinoma of the cervix: a retrospective analysis from a single institution. Br J Radiol, 2017. 90(1076): p. 20170241.
30. 31. Pearcey, R., M. Brundage, P. Drouin, et al., Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol, 2002. 20(4): p. 966-72.
31. 32. Calle, E.E., C. Rodriguez, K. Walker-Thurmond, and M.J. Thun, Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 2003. 348(17): p. 1625-38.
32. 33. Ko, C. and S. Chaudhry, The need for a multidisciplinary approach to cancer care. J Surg Res, 2002. 105(1): p. 53-7.
33. 34. Chen, R.J., D.Y. Chang, M.L. Yen, et al., Prognostic factors of primary adenocarcinoma of the uterine cervix. Gynecol Oncol, 1998. 69(2): p. 157-64.
34. 35. Kuo, H.Y., Z.Z. Lin, R. Kuo, et al., The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia. Oncologist, 2015. 20(9): p. 1051-7.
35. 36. J. Gross, E.D.D., J.B. Strauss, I. Helenowski, J. Lurain, E. Berry and N. Neubauer, Impact of Hyperglycemia in Patients With Cervical Cancer Treated With Definitive Chemoradiation on Overall Survival and Locoregional Control, in ASTRO's 57th annual meeting. 2015, Int. J. Rad. Oncol. Biol. Phy. p. S11.
36. 37. Giugliano, D., M.I. Maiorino, and K. Esposito, Linking prediabetes and cancer: a complex issue. Diabetologia, 2015. 58(1): p. 201-2.