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The fatigue rate and association with serum cytokine and leptin levels in breast cancer patients undergoing postmastectomy radiotherapy: a prospective evaluation

Year 2007, Volume: 22 Issue: 1, 1 - 12, 01.02.2007

Abstract

OBJECTIVES To investigate the fatigue rate during postmastectomy radiotherapy (RT) and the correlation between fatigue and serum cytokines and leptin levels. METHODS Thirty-eight, stage II-III breast cancer patients undergoing RT were evaluated with quality of life, Cancer Fatigue Scale, Visual Analogue Scale, Hospital Anxiety and Depression Scale, and the serum inflammatory cytokine and leptin levels were measured. The association of serum marker levels with fatigue was analyzed. RESULTS The fatigue rate increased during RT and decreased to pretreatment levels at 2 months following RT. Serum cytokine levels were not significantly changed with RT and was not found to be correlated with fatigue. Fatigue rate was found to be increased in cases with high leptin levels. A correlation was determined between preRT serum leptin levels and postRT fatigue rates (p=0.01). CONCLUSION It is found that fatigue increases during RT; fatigue is correlated with high serum leptin levels and decreases to pretreatment levels at 2 months following RT.

References

  • 1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55(1):10-30.
  • 2. O v e rgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997;337(14):949-55.
  • 3. Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353(9165):1641-8.
  • 4. Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005;97(2):116-26.
  • 5. Cancer related fatigue. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncologyv.1.2006.
  • 6. King KB, Nail LM, Kreamer K, Strohl RA, Johnson JE. Patients' descriptions of the experience of receiving radiation therapy. Oncol Nurs Forum 1985;12(4):55-61.
  • 7. Jacobsen PB, Thors CL. Fatigue in the radiation therapy patient: current management and investigations. Semin Radiat Oncol 2003;13(3):372-80.
  • 8. Greenberg DB, Gray JL, Mannix CM, Eisenthal S, Carey M. Treatment-related fatigue and serum interleukin-1 levels in patients during external beam irradiation for prostate cancer. J Pain Symptom Manage 1993;8(4):196- 200.
  • 9. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 2000;18(4):743-53.
  • 10. Glaus A. Fatigue in patients with cancer. Analysis and assessment. Recent Results Cancer Res 1998;145:I-XI, 1-172.
  • 11. Okuyama T, Akechi T, Kugaya A, Okamura H, Imoto S, Nakano T, et al. Factors correlated with fatigue in dis ease-free breast cancer patients: application of the Cancer Fatigue Scale. Support Care Cancer 2000;8(3):215-22.
  • 12. Okuyama T, Akechi T, Kugaya A, Okamura H, Shima Y, Maruguchi M, et al. Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 2000;19(1):5-14.
  • 13. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67(6):361-70.
  • 14. Moorey S, Greer S, Watson M, Gorman C, Rowden L, Tunmore R, et al. The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer. Br J Psychiatry 1991;158:255-9.
  • 15. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a qualityof-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85(5):365-76.
  • 16. Cella D, Peterman A, Passik S, Jacobsen P, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology (Williston Park) 1998;12(11A):369- 77.
  • 17. Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiotherapy-related fatigue. Crit Rev Oncol Hematol 2002;41(3):317-25.
  • 18. Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995;39(3):315-25.
  • 19. Smets EM, Visser MR, Willems-Groot AF, Garssen B, Oldenburger F, van Tienhoven G, et al. Fatigue and radiotherapy: (A) experience in patients underg o i n g treatment. Br J Cancer 1998;78(7):899-906.
  • 20. Smets EM, Visser MR, Willems-Groot AF, Garssen B, Schuster-Uitterhoeve AL, de Haes JC. Fatigue and radiotherapy: (B) experience in patients 9 months following treatment. Br J Cancer 1998;78(7):907-12.
  • 21. Greenberg DB, Sawicka J, Eisenthal S, Ross D. Fatigue syndrome due to localized radiation. J Pain Symptom Manage 1992;7(1):38-45.
  • 22. Irvine DM, Vincent L, Graydon JE, Bubela N. Fatigue in women with breast cancer receiving radiation therapy. Cancer Nurs 1998;21(2):127-35.
  • 23. Geinitz H, Zimmermann FB, Stoll P, Thamm R, K a ff e n b e rger W, Ansorg K, et al. Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer. Int J Radiat Oncol Biol Phys 2001;51(3):691-8.
  • 24. Donovan KA, Jacobsen PB, Andrykowski MA, Winters EM, Balducci L, Malik U, et al. Course of fatigue in women receiving chemotherapy and/or radiotherapy for early stage breast cancer. J Pain Symptom Manage 2004;28(4):373-80.
  • 25. Sadler IJ, Jacobsen PB. Progress in understanding fatigue associated with breast cancer treatment. Cancer Invest 2001;19(7):723-31.
  • 26. Kurzrock R. The role of cytokines in cancer-related fatigue. Cancer 2001;92(6 Suppl):1684-8.
  • 27. Rigas JR, Hoopes PJ, Meyer LA. Fatigue linked to plasma cytokines in patients with lung cancer undergoing combined modality therapy. Proc ASCO 1998;17:68A.
  • 28. Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 2002;64(4):604-11.
  • 29. Wratten C, Kilmurray J, Nash S, Seldon M, Hamilton CS, O'Brien PC, Denham JW. Fatigue during breast radiotherapy and its relationship to biological factors. Int J Radiat Oncol Biol Phys 2004;59(1):160-7.
  • 30. Akmansu M, Unsal D, Bora H, Elbeg S. Influence of locoregional radiation treatment on tumor necrosis factor-alpha and interleukin-6 in the serum of patients with head and neck cancer. Cytokine 2005;31(1):41-5.
  • 31. Agroyannis B, Kouvaris J, Tzanatos H, Chondros K, Stringou E, Damatopoulou A, et al. Influence of radiation treatment on serum transferrin and tumor necrosis factor-alpha. Anticancer Res 1992;12(5):1757-9.
  • 32. Tang JT, Yamazaki H, Nishimoto N, Inoue T, Nose T, Koizumi M, et al. Effect of radiotherapy on serum level of interleukin 6 in patients with cervical carcinoma. Anticancer Res 1996;16(4A):2005-8.
  • 33. Goodwin PJ, Ennis M, Fantus IG, Pritchard KI, Trudeau ME, Koo J, Hood N. Is leptin a mediator of adverse prognostic effects of obesity in breast cancer? J Clin Oncol 2005;23(25):6037-42.
  • 34. Somasundar P, Yu AK, Vona-Davis L, McFadden DW. Differential effects of leptin on cancer in vitro. J Surg Res 2003;113(1):50-5.
  • 35. Tartaglia LA. The leptin receptor. J Biol Chem 1997;272(10):6093-6.
  • 36. Somasundar P, McFadden DW, Hileman SM, VonaDavis L. Leptin is a growth factor in cancer. J Surg Res 2004;116(2):337-49.
  • 37. Piche T, Gelsi E, Schneider SM, Hebuterne X, Giudicelli J, Ferrua B, et al. Fatigue is associated with high circulating leptin levels in chronic hepatitis C. Gut 2002;51(3):434-9.
  • 38. Cleare AJ, O'Keane V, Miell J. Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low-dose hydrocortisone on leptin secretion. Clin Endocrinol (Oxf) 2001;55(1):113-9.
  • 39. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004;114(1):57-66.
  • 40. Luheshi GN, Gardner JD, Rushforth DA, Loudon AS, Rothwell NJ. Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci U S A 1999;96(12):7047-52.
  • 41. Licinio J, Mantzoros C, Negrao AB, Cizza G, Wong ML, Bongiorno PB, et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 1997;3(5):575-9.

Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme

Year 2007, Volume: 22 Issue: 1, 1 - 12, 01.02.2007

Abstract

AMAÇ Postmastektomi radyoterapi (RT) sırasında gelişen yorgunluğun derecesi ve yorgunluğun serum sitokinleri ve leptin düzeyleri ile ilişkisi araştırıldı. GEREÇ VE YÖNTEM Evre II-III meme kanseri tanısıyla RT programına alınan 38 olgu; RT başı, sonu ve RT sonrası ikinci ayda yaşam kalitesi, Kanser Yorgunluk Skalası ve Görsel Analog Skalası, Hastane Anksiyete ve Depresyon Skalası ile değerlendirildi; serum inflamatuvar sitokin ve leptin düzeyleri ölçüldü. Serum belirteç düzeylerinin yorgunlukla ilişkisi araştırıldı. BULGULAR Yorgunluk derecesi RT sırasında arttı ve RT sonrası ikinci ayda tedavi başı değerlere düştü. Serum sitokin düzeyleri RT'yle anlamlı değişmedi, yorgunlukla bağlantılı bulunmadı. Leptin düzeyi yüksek olanlarda daha fazla oranda yorgunluk saptandı. RT başındaki serum leptin düzeyleri ile RT sonu yorgunluk düzeyleri arasında bağlantı saptandı (p=0.01). SONUÇ Meme kanserli olgularda RT sırasında yorgunlukta artma olduğu, gelişen yorgunluğun yüksek serum leptin düzeyleri ile bağlantılı olduğu ve RT sonrası ikinci ayda tedavi öncesi değerlere düştüğü bulunmuştur.

References

  • 1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55(1):10-30.
  • 2. O v e rgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997;337(14):949-55.
  • 3. Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353(9165):1641-8.
  • 4. Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005;97(2):116-26.
  • 5. Cancer related fatigue. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncologyv.1.2006.
  • 6. King KB, Nail LM, Kreamer K, Strohl RA, Johnson JE. Patients' descriptions of the experience of receiving radiation therapy. Oncol Nurs Forum 1985;12(4):55-61.
  • 7. Jacobsen PB, Thors CL. Fatigue in the radiation therapy patient: current management and investigations. Semin Radiat Oncol 2003;13(3):372-80.
  • 8. Greenberg DB, Gray JL, Mannix CM, Eisenthal S, Carey M. Treatment-related fatigue and serum interleukin-1 levels in patients during external beam irradiation for prostate cancer. J Pain Symptom Manage 1993;8(4):196- 200.
  • 9. Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 2000;18(4):743-53.
  • 10. Glaus A. Fatigue in patients with cancer. Analysis and assessment. Recent Results Cancer Res 1998;145:I-XI, 1-172.
  • 11. Okuyama T, Akechi T, Kugaya A, Okamura H, Imoto S, Nakano T, et al. Factors correlated with fatigue in dis ease-free breast cancer patients: application of the Cancer Fatigue Scale. Support Care Cancer 2000;8(3):215-22.
  • 12. Okuyama T, Akechi T, Kugaya A, Okamura H, Shima Y, Maruguchi M, et al. Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 2000;19(1):5-14.
  • 13. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67(6):361-70.
  • 14. Moorey S, Greer S, Watson M, Gorman C, Rowden L, Tunmore R, et al. The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer. Br J Psychiatry 1991;158:255-9.
  • 15. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a qualityof-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85(5):365-76.
  • 16. Cella D, Peterman A, Passik S, Jacobsen P, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology (Williston Park) 1998;12(11A):369- 77.
  • 17. Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiotherapy-related fatigue. Crit Rev Oncol Hematol 2002;41(3):317-25.
  • 18. Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995;39(3):315-25.
  • 19. Smets EM, Visser MR, Willems-Groot AF, Garssen B, Oldenburger F, van Tienhoven G, et al. Fatigue and radiotherapy: (A) experience in patients underg o i n g treatment. Br J Cancer 1998;78(7):899-906.
  • 20. Smets EM, Visser MR, Willems-Groot AF, Garssen B, Schuster-Uitterhoeve AL, de Haes JC. Fatigue and radiotherapy: (B) experience in patients 9 months following treatment. Br J Cancer 1998;78(7):907-12.
  • 21. Greenberg DB, Sawicka J, Eisenthal S, Ross D. Fatigue syndrome due to localized radiation. J Pain Symptom Manage 1992;7(1):38-45.
  • 22. Irvine DM, Vincent L, Graydon JE, Bubela N. Fatigue in women with breast cancer receiving radiation therapy. Cancer Nurs 1998;21(2):127-35.
  • 23. Geinitz H, Zimmermann FB, Stoll P, Thamm R, K a ff e n b e rger W, Ansorg K, et al. Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer. Int J Radiat Oncol Biol Phys 2001;51(3):691-8.
  • 24. Donovan KA, Jacobsen PB, Andrykowski MA, Winters EM, Balducci L, Malik U, et al. Course of fatigue in women receiving chemotherapy and/or radiotherapy for early stage breast cancer. J Pain Symptom Manage 2004;28(4):373-80.
  • 25. Sadler IJ, Jacobsen PB. Progress in understanding fatigue associated with breast cancer treatment. Cancer Invest 2001;19(7):723-31.
  • 26. Kurzrock R. The role of cytokines in cancer-related fatigue. Cancer 2001;92(6 Suppl):1684-8.
  • 27. Rigas JR, Hoopes PJ, Meyer LA. Fatigue linked to plasma cytokines in patients with lung cancer undergoing combined modality therapy. Proc ASCO 1998;17:68A.
  • 28. Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 2002;64(4):604-11.
  • 29. Wratten C, Kilmurray J, Nash S, Seldon M, Hamilton CS, O'Brien PC, Denham JW. Fatigue during breast radiotherapy and its relationship to biological factors. Int J Radiat Oncol Biol Phys 2004;59(1):160-7.
  • 30. Akmansu M, Unsal D, Bora H, Elbeg S. Influence of locoregional radiation treatment on tumor necrosis factor-alpha and interleukin-6 in the serum of patients with head and neck cancer. Cytokine 2005;31(1):41-5.
  • 31. Agroyannis B, Kouvaris J, Tzanatos H, Chondros K, Stringou E, Damatopoulou A, et al. Influence of radiation treatment on serum transferrin and tumor necrosis factor-alpha. Anticancer Res 1992;12(5):1757-9.
  • 32. Tang JT, Yamazaki H, Nishimoto N, Inoue T, Nose T, Koizumi M, et al. Effect of radiotherapy on serum level of interleukin 6 in patients with cervical carcinoma. Anticancer Res 1996;16(4A):2005-8.
  • 33. Goodwin PJ, Ennis M, Fantus IG, Pritchard KI, Trudeau ME, Koo J, Hood N. Is leptin a mediator of adverse prognostic effects of obesity in breast cancer? J Clin Oncol 2005;23(25):6037-42.
  • 34. Somasundar P, Yu AK, Vona-Davis L, McFadden DW. Differential effects of leptin on cancer in vitro. J Surg Res 2003;113(1):50-5.
  • 35. Tartaglia LA. The leptin receptor. J Biol Chem 1997;272(10):6093-6.
  • 36. Somasundar P, McFadden DW, Hileman SM, VonaDavis L. Leptin is a growth factor in cancer. J Surg Res 2004;116(2):337-49.
  • 37. Piche T, Gelsi E, Schneider SM, Hebuterne X, Giudicelli J, Ferrua B, et al. Fatigue is associated with high circulating leptin levels in chronic hepatitis C. Gut 2002;51(3):434-9.
  • 38. Cleare AJ, O'Keane V, Miell J. Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the effects of low-dose hydrocortisone on leptin secretion. Clin Endocrinol (Oxf) 2001;55(1):113-9.
  • 39. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 2004;114(1):57-66.
  • 40. Luheshi GN, Gardner JD, Rushforth DA, Loudon AS, Rothwell NJ. Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci U S A 1999;96(12):7047-52.
  • 41. Licinio J, Mantzoros C, Negrao AB, Cizza G, Wong ML, Bongiorno PB, et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 1997;3(5):575-9.
There are 41 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Diclehan Ünsal This is me

Atınç Aksu This is me

Ümit Bağrıaçık This is me

Müge Akmansu This is me

Publication Date February 1, 2007
Published in Issue Year 2007 Volume: 22 Issue: 1

Cite

APA Ünsal, D., Aksu, A., Bağrıaçık, Ü., Akmansu, M. (2007). Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme. Türk Onkoloji Dergisi, 22(1), 1-12.
AMA Ünsal D, Aksu A, Bağrıaçık Ü, Akmansu M. Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme. Türk Onkoloji Dergisi. February 2007;22(1):1-12.
Chicago Ünsal, Diclehan, Atınç Aksu, Ümit Bağrıaçık, and Müge Akmansu. “Postmastektomi Radyoterapi Uygulanan Meme Kanserli Olgularda gelişen yorgunluğun Derecesi, Serum Sitokin Ve Leptin düzeyleri Ile ilişkisi: Prospektif değerlendirme”. Türk Onkoloji Dergisi 22, no. 1 (February 2007): 1-12.
EndNote Ünsal D, Aksu A, Bağrıaçık Ü, Akmansu M (February 1, 2007) Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme. Türk Onkoloji Dergisi 22 1 1–12.
IEEE D. Ünsal, A. Aksu, Ü. Bağrıaçık, and M. Akmansu, “Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme”, Türk Onkoloji Dergisi, vol. 22, no. 1, pp. 1–12, 2007.
ISNAD Ünsal, Diclehan et al. “Postmastektomi Radyoterapi Uygulanan Meme Kanserli Olgularda gelişen yorgunluğun Derecesi, Serum Sitokin Ve Leptin düzeyleri Ile ilişkisi: Prospektif değerlendirme”. Türk Onkoloji Dergisi 22/1 (February 2007), 1-12.
JAMA Ünsal D, Aksu A, Bağrıaçık Ü, Akmansu M. Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme. Türk Onkoloji Dergisi. 2007;22:1–12.
MLA Ünsal, Diclehan et al. “Postmastektomi Radyoterapi Uygulanan Meme Kanserli Olgularda gelişen yorgunluğun Derecesi, Serum Sitokin Ve Leptin düzeyleri Ile ilişkisi: Prospektif değerlendirme”. Türk Onkoloji Dergisi, vol. 22, no. 1, 2007, pp. 1-12.
Vancouver Ünsal D, Aksu A, Bağrıaçık Ü, Akmansu M. Postmastektomi radyoterapi uygulanan meme kanserli olgularda gelişen yorgunluğun derecesi, serum sitokin ve leptin düzeyleri ile ilişkisi: Prospektif değerlendirme. Türk Onkoloji Dergisi. 2007;22(1):1-12.