The role of dose volume histograms and TGF-β in the prediction of radiation pneumonitis: a pilot study

Year 2008, Volume: 23 Issue: 3, 109 - 119, 01.04.2008

Banu Atalar Fazilet Öner Dinçbaş Seval Aydın Hafize Uzun Sedat Koca

Abstract

OBJECTIVES To evaluate the role of some parameters of dose volume histograms (DVH) and plasma TGF-β levels in predicting radiation pneumonitis in non-small cell lung cancer (NSCLC) patients. METHODS Fifteen NSCLC patients treated with 3D conformal radiotherapy were included in the study. Radiotherapy dose was a median 60 Gy. Mean lung dose (MLD), V20 and V30 were calculated from both ipsilateral and contralateral lung DVH. TGF-β levels were studied with ELISA. RESULTS Median follow-up was 16 months (range 10-55). Radiation pneumonitis was diagnosed in three patients (6, 9, 12 months). Dose parameters of ipsi- and contralateral lungs revealed that higher MLD, V20, V30 values in contralateral lung were statistically significant for pneumonitis (p

Keywords

Transforming Growth Factor beta, Radiation Pneumonitis, Radiotherapy, Conformal, Radiotherapy Dosage

Radyasyon pnömonisinin öngörülmesinde doz volüm histogramları ve TGF-β'nın yeri: Pilot çalışma

Abstract

AMAÇ Torasik radyoterapi uygulanan küçük hücreli olmayan akciğer kanserli (KHOAK) hastalarda, radyasyon pnömonisi riski ile doz volüm histogramları (DVH) parametreleri ve plazma T G F -βseviyelerinin korelasyonu araştırıldı. GEREÇ VE YÖNTEM Bu çalışmaya üç boyutlu konformal radyoterapi uygulanan 15 KHOAK hastası dahil edildi. Radyoterapi dozu 50-66 Gy arası nda değişmekte olup, medyan doz 60 Gy idi. Olguların tümünde ipsilateral ve kontrlateral akciğerler için DVH'larından elde edilen MLD, V20, V30 değerleri incelendi. TGF-β seviyeleri ELISA yöntemi ile değerlendirildi. BULGULAR Olguların medyan takip süresi 16 ay idi (aralık 6-55). Bu süre içerisinde radyasyon pnömonisi üç olguda saptandı (1.,6. ve 9. aylarda). İpsilateral ve kontrlateral akciğerlerin doz par am e tr el eri karşılaştırıldığında, kontrlateral akciğ erlerin MLD, V20 ve V30 değerlerinin yüksek oluşu pnömoni gelişimi açısından anlamlı bulundu (p < 0,005). TGF-β seviyeleri pnömoni gelişimi için anlamlı bulunmadı. SONUÇ Yüksek kontrlateral akciğer dozunun (MLD, V2 0, V3 0) radyasyon pnömonisi gelifliminde risk faktörü olabileceği gösterilmiştir. TGF-β seviyeleri radyoterapi sonrası erken dönemde pnömoni riskini göstermede faydalı olmamıştır.

Keywords

Doz volüm histogramı, radyasyon pnömonisi, MLD, V20, V20, TGF-β

References

• 1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1997. CA Cancer J Clin 1997;47(1):5-27.
• 2. Murphy TP, Casey MT. Determination of operability in candidates who undergo lung resection for bronchogenic carcinoma. Can J Surg 1990;33(6):470-3.
• 3. Perez C, Azarnia N, Cox J. Sequela of definitive irradiation in the treatment of carcinoma of the lung. In: Motta G, editor. Lung cancer: advanced concepts and present status. Genoa, Italy: G Motta Publishing; 1989.
• 4. Emami B, Graham MV. Lung. In: Perez CA, Brady LW, editors. Principles and practice of radiation oncology. Philadelphia, New York: Lippincott-Raven; 1998. p. 1181-220.
• 5. Armstrong JG, Burman C, Leibel S, Fontenla D, Kutcher G, Zelefsky M, et al. Three-dimensional conformal radiation therapy may improve the therapeutic ratio of high dose radiation therapy for lung cancer. Int J Radiat Oncol Biol Phys 1993;26(4):685-9.
• 6. Martel MK, Ten Haken RK, Hazuka MB, Turrisi AT, Fraass BA, Lichter AS. Dose-volume histogram and 3-D treatment planning evaluation of patients with pneumonitis. Int J Radiat Oncol Biol Phys 1994;28(3):575-81.
• 7. Langer M, Kijewski P. CCRT (computer controlled radiation therapy) for non-small cell lung cancer: sensitivity of clinical gains to organ tolerance restrictions. Int J Radiat Oncol Biol Phys 1992;22(2):325-32.
• 8. Marks LB, Munley MT, Bentel GC, Zhou SM, Hollis D, Scarfone C, et al. Physical and biological predictors of changes in whole-lung function following thoracic irradiation. Int J Radiat Oncol Biol Phys 1997;39(3):563-70.
• 9. Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 1995;33(1):99-109.
• 10. Franklin TJ. Therapeutic approaches to organ fibrosis. Int J Biochem Cell Biol 1997;29(1):79-89.
• 11. Grande JP. Role of transforming growth factor-beta in tissue injury and repair. Proc Soc Exp Biol Med 1997;214(1):27-40.
• 12. Anscher MS, Kong FM, Jirtle RL. The relevance of transforming growth factor beta 1 in pulmonary injury after radiation therapy. Lung Cancer 1998;19(2):109-20.
• 13.Rodemann HP, Bamberg M. Cellular basis of radiationinduced fibrosis. Radiother Oncol 1995;35(2):83-90.
• 14. Hakenjos L, Bamberg M, Rodemann HP. TGF-beta1- mediated alterations of rat lung fibroblast differentiation resulting in the radiation-induced fibrotic phenotype. Int J Radiat Biol 2000;76(4):503-9.
• 15. Martin M, Lefaix J, Delanian S. TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys 2000;47(2):277-90.
• 16. Travis EL. Organizational response of normal tissues to irradiation. Semin Radiat Oncol 2001;11(3):184- 96.
• 17. Anscher MS, Murase T, Prescott DM, Marks LB, Reisenbichler H, Bentel GC, et al. Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis. Int J Radiat Oncol Biol Phys 1994;30(3):671-6.
• 18.Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31(5):1341-6.
• 19. Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for nonsmall cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999;45(2):323-9.
• 20.Byhardt RW, Martin L, Pajak TF, Shin KH, Emami B, Cox JD. The influence of field size and other treatment factors on pulmonary toxicity following hyperfractionated irradiation for inoperable non-small cell lung cancer (NSCLC)-analysis of a Radiation Therapy Oncology Group (RTOG) protocol. Int J Radiat Oncol Biol Phys 1993;27(3):537-44.
• 21. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21(1):109-22.
• 22. Kutcher GJ, Burman C. Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method. Int J Radiat Oncol Biol Phys 1989;16(6):1623-30.
• 23. Kutcher GJ, Burman C, Brewster L, Goitein M, Mohan R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int J Radiat Oncol Biol Phys 1991;21(1):137-46.
• 24. Lyman JT, Wolbarst AB. Optimization of radiation therapy, IV: A dose-volume histogram reduction algorithm. Int J Radiat Oncol Biol Phys 1989;17(2):433-6.
• 25. Oetzel D, Schraube P, Hensley F, Sroka-Pérez G, Menke M, Flentje M. Estimation of pneumonitis risk in three-dimensional treatment planning using dosevolume histogram analysis. Int J Radiat Oncol Biol Phys 1995;33(2):455-60.
• 26. Yorke ED, Jackson A, Rosenzweig KE, Merrick SA, Gabrys D, Venkatraman ES, et al. Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys 2002;54(2):329-39.
• 27. Armstrong JG, Zelefsky MJ, Leibel SA, Burman C, Han C, Harrison LB, et al. Strategy for dose escalation using 3-dimensional conformal radiation therapy for lung cancer. Ann Oncol 1995;6(7):693-7.
• 28. Hernando ML, Marks LB, Bentel GC, Zhou SM, Hollis D, Das SK, et al. Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys 2001;51(3):650-9.
• 29. Sunyach MP, Falchero L, Pommier P, Perol M, Arpin D, Vincent M, et al. Prospective evaluation of early lung toxicity following three-dimensional conformal radiation therapy in non-small-cell lung cancer: preliminary results. Int J Radiat Oncol Biol Phys 2000;48(2):459-63.
• 30.Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys 1992;24(1):93-101.
• 31. Anscher MS, Kong FM, Andrews K, Clough R, Marks LB, Bentel G, et al. Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 1998;41(5):1029-35.
• 32. Fan M, Marks LB, Hollis D, Bentel GG, Anscher MS, Sibley G, et al. Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction? J Clin Oncol 2001;19(2):543-50.
• 33. Anscher MS, Marks LB, Shafman TD, Clough R, Huang H, Tisch A, et al. Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic r a d i o t h e r a p y. Int J Radiat Oncol Biol Phys 2003;56(4):988-95.
• 34. De Jaeger K, Seppenwoolde Y, Kampinga HH, Boersma LJ, Belderbos JS, Lebesque JV. Significance of plasma transforming growth factor-beta levels in radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;58(5):1378-87.