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1 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, , * * Comparative Study Between Respiratory Gated Conventional 2-D Plan and 3-D Conformal Plan for Predicting Radiation Hepatitis Sang-wook Lee, MD, Gwi Eon Kim, MD, Kap Soo Chung, PhD*, Chang Geol Lee, MD, Jinsil Seong MD and Chang Ok Suh, MD Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University, College of Medicine, Department of Radiology *, Seoul Health College, Seoul, Korea Purpose : To evaluate influences associated with radiation treatment planning obtained with the patient breathing freely Material and Methods : We compared reduction or elimination of planning target volume (PTV) margins with 2-D conventional plan with inclusion of PTV margins associated with breathing with 3-D conformal therapy The respiratory non gated 3-D conformal treatment plans were compared with respiratory gated conventional 2-D plans in 4 patients with hepatocellular carcinomas Isodose distribution, dose statistics, and dose volume histogram (DVH) of PTVs were used to evaluate differences between respiratory gated conventional 2-D plans and respiratory non gated 3-D conformal treatment plans In addition, the risk of radiation exposure of surrounding normal liver and organs are evaluated by means of DVH and normal tissue complication probabilities (NTCPs) Results : The vertical movement of liver ranged 2-3 cm in all patients We found no difference between respiratory gated 2-D plans and 3-D conformal treatment plans with the patients breathing freely Treatment planning using DVH analysis of PTV and the normal liver was used for all patients DVH and calculated NTCP showed no difference in respiratory gated 2-D plans and respiratory non gated 3-D conformal treatment plans Conclusion : Respiratory gated radiation therapy was very important in hepatic tumors because radiation induced hepatitis was dependent on remaining normal liver volume Further investigational studies for respiratory gated radiation treatment combined with 3-D conformal treatment are required Key Words : 3-D conformal therapy, Hepatocellular carcinoma

2 1) 3-18, 19) 3-2, 3), 21),,,, I 131 Lipiodol cm, 12), 4-8) 9-13) 30 Gy, 35 Gy 22, 23), 10,14) (respiratory gated radiation therapy)3-12, 15-17), 12, 13) 2-, (respiratory gated conventional radiation therapy), 4 (box technique), 3 3- (respiratory non gated 3-D conformal, radiation therapy), 3-,

3 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, cm, 11 cm 5 8, 7 cm 6 7, 3 4 cm 26) 3- (Pinnacle 3, ADAC co, USA) 2, cm 2-3 cm 5-10,, 24) (Fig 1) 55 Gy Liver Boundary 0 border 1 border 2 borders PTV Fig 1 Classification of tumor location in the liver surface 3-, 3- normal tissue complication probability (NTCP) 3 (simulation) (isocenter) 25) 2-3 mm ICRU 50 (planning target volume) 27) setup (Fig 2), (Beam s eye view) 5 (wedge) 3- (pencil beam) (convolution algorithm)

4 Liver Motion by Breathing PTV Breathing Margins CTV +SE,, 4 NTCP NTCP LymanNTCP 28) (3) (3) n (volume effect) n S- NTCP (1) Fig 2 Planning target volume (PTV) expansions for patient breathing applied to the superior and inferior borders of the clinical target volume (CTV), with already includes PTV margins for setup error (SE) NTCP= { 1} over { SQRT { 2 pi } } INT _{ t}^{ -INF } t CDOT exp (- { t}^{2 }/2)dt (1) v= { V} /{ { V}_{ref } } (2) TD (v)= { TD (1)} CDOT { { v}^{-n} } (3) t= { (D- { TD}_{50 } (v)) }/{ (m CDOT { TD}_{50 } (v)) } (4) S- (biological index) TD (1), TD (v) 2 (v) (clinical target volume, CTV) TD 50 (1) setup 5 50% TD 50 (v) 3 v 50% (2) v, Vref diffuse disease power law n 12)

$J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998 (fitted) { v}_{ eff} = DELTA { v}_{max }+ DELTA { v}_{1 } { (D_1}/ D_max) }^{1/n }+DELTA { v}_{2 } { (D_2/ D_ max ) }^{1/n } + TD 50 (v)$

5 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998 (fitted) { v}_{ eff} = DELTA { v}_{max }+ DELTA { v}_{1 } { (D_1}/ D_max) }^{1/n }+DELTA { v}_{2 } { (D_2/ D_ max ) }^{1/n } + TD 50 (v) (4) V_eff SUM left{v_i (D_i / D_ref )^1/n right}(6) t (4)m (5) (6) - S- TD 50 29) (2) v v (3) n, m, TD 50 (1) TD 50 (v) TD 50 (v), v, m (4) (4) t vd t (1)t NTCP v D 17) TD 50 (1)Emami 40Gy m Burman 33) 015 n Lawrence, 069 NTCP NTCP 30) Linear interpolation 31, Effective volume 32) NTCP Effective volume 31) 2- Effective volume x (D ref) (D max) y V eff Veff 1 15) D ref V eff 1 vi Di power law D max veff (5) 31) 12) n (coplanar),,,,

7 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998, 1 (Volumetric Analysis) 2 (PTV: planning terget volume) (Fig 3) 301cc 2-100% 95%, 301cc 3% (Table 1) (Fig 4) cgy cgy cgy

9 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, cgy 5% 95% (D 95)1725 cgy1975 cgy 3-, (D 05)

10 95% (Table 3), (Fig 5) % (Table 2) 3, ,

11 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998 NTCP (Table 4) Fig 6 30% Gy () 9-11), 12, 13, 15, 16, 34) 29) 10, 14) 16, 27)

12 2-3cm, 12% NTCP 15% 35) 22, 23) 36) 3-,, 19, 25) 2-3cm,, setup 37) 3-3- Michigan 2-3cm 12) 3-3-, 38) 20) 3-, (box) 25) 2-3- () 3% 2- NTCP ) NTCP,

13 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998, 5 5%50%, 3-, 39, 40),, 31) th ed Philadelphia: Lippincott Co 1993; ) NTCP 05 50%primary carcinoma of the liver Cancer Treat Rev 1977; 4: NTCP NTCP 3% Kim IS, Kim HJ, Oh HC, et al The cancer registry program in Kangwha country, the first report Korean J Epidemiol 1984; 6: Lotze MT, Flickinger JC, Carr BI Hepatobiliary neoplasms In : DeVita VT, Hellman S, Rosenberg SA, eds Cancer principles & practice of oncology 3 Ringe B, Pichlmayr R, Wittekind C, Tusch G Surgical treatment of hepatocellular carcinoma: Experience with liver resection and transplantation in 198 patients World J Surg 1991; 15: Lee Y-T N Systemic and regional treatment of 5 Sasaki Y, Imaoka S, Kasugai H et al A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge Cancer 1987; 60: Shijo H, Okaazaki M, Higashihara H, et al Hepatocellular carcinoma: a multivariate analysis of prognostic features in patients treated with hepatic arterial embolization Am J Gastroentrol 1992; 87: Yu YQ, Xu DB, Zhang WZ, Yuan YF, Li GH Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy J Cancer Res Clin Oncol 1995; 121: Guthrie CM, Leahy AL, Redhead DN, Garden OJ Transcatheter hepatic arterial therapy for symptomatic liver malignancy J Royal Coll Surg Edinhurgh 1991; 36: , 9 Haddad E, Le Bourgeois JP, Kuentz M, Lobo P Liver complications in lymphomas treated with a combination of combination of chemotherapy and radiotherapy preliminary results Int J Radiat Oncol Biol Phys 1983; 9: Kim TH, Pannahon AM, Friedman M, Webster JH Acute transient radiation hepatitis following whole liver irradiation Clin Radiol 1976; 27: Poussin-Rosillo H, Nisce LZ, D'Angio GJ Hepatic radiation tolerance in Hodgkin's Disease patients Radiology 1976; 121: Lawrence TS, Ten Haken RK, Kessler ML, et al The use of 3-D dose volume analysis to predict radiation hepatitis Int J Radiat Oncol Biol Phys 1992;

14 23: Cohen L The tissue-volume factor in radiation oncology Int J Radiat Oncol Biol Phys 1982; 8: Ingold JA, Reed GB, Kaplan HS, Bagshaw MA Radiation hepatitis Am J Roentgenol 1965; 93: Ten Hanken RK, Martel MK, Kessler ML, et al Use of Veff and iso-ntcp in the implementation of dose escalation protocols Int J Radiat Oncol Biol Phys 1993; 27: Lawrence TS, Tesser RJ, Ten Hanken RK An application of dose volume histograms to the treatment of intrahepatic malignancies with radiation therapy Int J Radiat Oncol Biol Phys 1990; 19: Emami B, Lyman J, Brown A, et al Tolerance of normal tissue to therapeutic irradiation Int J Radiat Oncol Biol Phys 1991; 21: Ten Hanken RK, Lawrence TS, McShan DL, Tesser RJ, Fraass BA, Lichter AS Technical considerations in the use of 3-D beam arrangements in the abdomen Radiother Oncol 1991; 22: Lee SW, Oh YT, Kim WC, et al Dosimetric characteristics on penumbra regions of the multileaf collimator as compared with the lead alloy block J Korean Soc Ther Radiol 1995; 13: Robertson JM, Lawrence TS, Dworzanin LM, et al Long-term results of hepatic artery fluorodeoxyurididne and conformal radiation therapy for primary hepatobiliary cancers Int J Radiat Oncol Biol Phys 1997; 37: Ten Haken RK, Lam KL, Balter JM, Robertson JM, Hazuka MB, Andrews JC Assessment of liver and lung motion for conformal therapy using radiopaque markers Med Phys 1993; 20: Kubo HD, Hill BC Respiration gated radiotherapy treatment: a technical study Phy Med Biol 1996; 41: Ohara K, Okumura T, Akisada M, et al Irradiation synchronized with respiration gate Int J Radiat Oncol Biol Phys 1989; 17: Ten Haken RK, Balter JM, Marsh LH, Robertson JM, Lawrence TS Potential benefits of eliminating planning target volume expansions for patient breathing in the treatment of liver tumors Int J Radiat Oncol Biol Phys 1997; 38: Niemieko A, Goiten M Calculation of normal tissue complication probability and dose-volume histogram relation schemes for tissues with a critical element architecture Radiother Oncol 1991; 20: Lee SW, Kim GE, Keum KC, et al Clinical application of 3-D conformal radiotherapy for carcinoma of the ethmoid sinus: Comparative analysis between conventional 2-D and 3-D conformal plans J Korean Soc Ther Radiol 1997; 15: ICRU Report 50 Prescribing, Recording, and Reporting Photon Beam Therapy International Commission on Radiation Units and Measurements, Bethesda, MD, Lyman JT Complication probability as assessed from dose-volume histograms Radiat Res 1985; 104:S-13-S Jackson A, Ten Haken RK, Robertson JM, Kessler ML, Kutcher GJ, Lawrence TS Analysis of clinical complication data for radiation hepatitis using a parallel architecture model Int J Radiat Oncol Biol Phys 1995; 31: Lyman JT, Wolbarst AB Optimization of radiation therapy, : A method of assessing complication probabilities from dose-volume histograms Int J Radiat Oncol Biol Phys 1987; 13: Kutcher GJ, Burman C Calculation of complication probability factors for nonuniform normal tissue irradiation: the effective volume method Int J Radiat Oncol Biol Phys 1989; 16: Kutcher GJ, Burman C, Brewster L, Goitein M, Mohan R Histogram reduction methods for calculation complication probabilities for 3D treatment planning evaluations Int J Radiat Oncol Biol Phys 1991; 21: Burman C, Kutcher GJ, Emami B, Goiten M Fitting of normal tissue tolerance data to an analytic function Int J Radiat Oncol Biol Phys 1991; 21: Lawrence TS, Dworzanin LM, Walker-Andrews SC, et al Treatment of cancers involving the liver and porta hepatis with external beam irradiation and intraarterial hepatic fluorodeoxyuridine Int J Radiat Oncol Biol Phys 1990; 20: Balter JM, Ten Haken RK, Lawrence TS, Lam KL, Robertson JM Uncertainties in CT-based radiation therapy treatment planning associated with patient breathing Int J Radiat Oncol Biol Phys 1996; 36: Jones KR A respiration monitor for use with CT body scanning and other imaging techniques Br J Radiol 1982; 55: Urie MM, Goitein M, Doppke K, et al The role of uncertainty analysis in treatment planning Int J Radiat Oncol Biol Phys 1991; 21: Robertson JM, Lawrence TS, Dworzanin LM, et al Treatment of primary hepatobiliary cancer with conformal radiation therapy and regional chemotherapy Journal of Clinical Oncology 1993; 11: Emami B, Lyman J, Brown A, et al Tolerance of normal tissue to therapeutic irradiation NCI Contract Report for N01-CM-47316, N01-CM-47695, N01- CM and N01-CM Rubin P, Casarett G A direction for clinical radiation pathology the tolerance dose In: Vaeth JM, ed, Frontiers of Radiation Therapy and Oncology Vol 6 Baltimore: University Park Press 1972;1-16

15 J Korean Soc Ther Radiol Oncol : Vol 16, No 4, December, 1998 = = *,

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