Clinical Experiences of CK/HT in Hepatocellular Carcinoma

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Chul-Seung Kay1,3 , Seok-Hyun Son1, Myung-Soo Kim1, Jung-Hyun Kwon2
Department of Radiation Oncology1 & 2Internal Medicine2
3Catholic Comprehensive Hospital for Advanced Cancer3
Incheon St. Mary Hospital
The Catholic University of Korea

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Clinical Experiences of CK/HT in Hepatocellular Carcinoma

  1. 1. Clinical Experiences of CK/HT in Hepatocellular Carcinoma Chul-Seung Kay1,3 , Seok-Hyun Son1, Myung-Soo Kim1, Jung-Hyun Kwon2 Department of Radiation Oncology1 & 2Internal Medicine2 3Catholic Comprehensive Hospital for Advanced Cancer3 Incheon St. Mary Hospital The Catholic University of Korea
  2. 2. Contents • The treatment outcome after CK • The treatment outcome after HT • The application of our data in HCC • Ongoing investigation
  3. 3. Experience of CK in CMC
  4. 4. • Retrospective study to evaluate the efficacy of SBRT for small non-resectable HCC and SBRT combined with TACE for advanced HCC with PVTT • 32 HCC lesions of 31 patients - 23 lesions of 22 patients treated targeting small HCC - 9 lesions of 9 patients targeting PVTT (all the patients received TACE for advanced HCC) • Median tumor volume was 25.2 ml (range, 3.6 ~ 57.3 ml) • SBRT dose 30-39 Gy (median 36 Gy) in 3 fractions for consecutive days • 75-85% of the PTV (GTV + 0.5cm) Choi BO et al BMC cancer 8:351, 2008
  5. 5. Inclusion criteria 1. Histologically proven 2. Active enhancing HCC by CT 3. PVTT near the HCC 4. No extrahepatic mets 5. Max diameter ≤ 5cm 6. Age < 75 years old 7. HCC that did not developed within transplanted liver 8. ECOG < 3 9. No prev Hx of RT 10. Wbc > 4000, PLT > 50,000 Median FU: 10.5 months FU range: 2.0-18.5 months Choi BO et al BMC cancer 8:351, 2008
  6. 6. Choi BO et al BMC cancer 8:351, 2008
  7. 7. Median Survival 1 year survival rate Small HCC (n=22) 12 months 88.1% PVTT (n=9) 8 months 43.2% All (n=31) 11.5 months 81.4% Choi BO et al BMC cancer 8:351, 2008
  8. 8. Toxicity 1. Grade 3 liver enzyme toxicity was in one patient 2. Progression of CP class from A to B within 3 months was in 5 patients. Three of them had progressive disease in 1-2 months after SBRT 3. No progression from CP class B after SBRT 4. No hematologic toxicity over grade 2 was found. 5. No grade 3 or greater GI toxicity including nausea was found. Choi et al BMC cancer 8:351, 2008
  9. 9. • Retrospective study to evaluate the long term effect of SBRT for primary small HCC ineligible for local therapy or surgery • 42 HCC patients with tumor < 100 ml (median tumor volume 15.4 ml; range, 3.0- 81.8ml) • SBRT 30-39Gy/3fx/3days (median 80%, range 70-85%) • median FU duration 28.7 months (range, 8.4-49.1 months) Kwon JH et al BMC cancer 10:475, 2010
  10. 10. Kwon JH et al BMC cancer 10:475, 2010 • Flow of study participant in the study
  11. 11. Kwon et al BMC cancer 10:475, 2010 a) A case of CR, b) a case of PR, c) a case of SD •The dotted iosdosel line represents GTV •The green, yellow and purple curves the 75, 70 and 10% isodose line, respectively. •36Gy was prescribed on the 75% isodose line. •Axial, coronal, and sagittal views and DVH of the tumor and liver are demonstarated
  12. 12. Kwon JH et al BMC cancer 10:475, 2010
  13. 13. Kwon JH et al BMC cancer 10:475, 2010 • Pattern of disease recurrence CR; complete response PD; progressive disease 28.6% Intrahepatic PD; 59.5%
  14. 14. Son SH et al. Int J Radiat Oncol Biol Phys. 2010:78;1073-1080 • Identification of the parameters to predict hepatic toxicity and deterioration of liver function • Retrospective analysis of 47 small HCCs patients treated with CK • Gross tumor volume 18.3±15.9cc (range, 3.0-81.3cc) • Total dose 30-39 Gy/3fx (median 36 Gy)
  15. 15. Son SH et al. Int J Radiat Oncol Biol Phys. 2010:78;1073-1080
  16. 16. Son SH et al. Int J Radiat Oncol Biol Phys. 2010:78;1073-1080
  17. 17. AUC 0.997 P = 0.002
  18. 18. Experiences of HT in CMC
  19. 19. Jang JW et al. Int J Radiat Oncol Biol Phys. 2009:74;412-8 50 Gy/10 fractions/2 weeks
  20. 20. • Total 42 patients with HCC & extrahepatic metastases • Total Number of lesions : 152 (3.5/person) • Helical Tomotherapy for the lesions upto median 50Gy/10fx/2weeks • TACL with epirubicin and CDDP for intrahepatic lesion following RT • Overall response rate * CR was achieved in 26.3% and 5.0% in pulmonary and adrenal metastases, respectively. • Overall survival rate at 1 year and 2 years : 50.1% and 14.9% • Median survival : 12.3 months • Acturial in-field control rate (within 1 year) : 79% • No grade 4 or 5 treatment related toxicity intrahepatic tumor pulmonary metastases LN/adrenal metastases soft tissue metastases 45.2% 68.4% 60.0% 66.7% Jang JW et al. Int J Radiat Oncol Biol Phys. 2009:74;412-8
  21. 21. 6 months 12 months 18 months 24 months Median OSR 75.2% 50.1% 19.9% 14.9% 12.3 months OPF S 42.7% 9.6% 10.5 months IPFS 79.0% 61.5% Helical Tomotherapy is safe and feasible without major toxicities for the treatment of advanced HCC and results in excellent local control and a potential survival benefit. Jang JW et al. Int J Radiat Oncol Biol Phys. 2009:74;412-8
  22. 22. Kim JY et al Radiat Oncol 8:15, 2013
  23. 23. Inclusion criteria 1. Age > 18 yeas old 2. Tumor thrombosis in main and 1st or 2nd order branch of portal vein 3. 3 or less JIS score 4. Child-pugh class A or B 5. No extrahepatic metastases 6. Refractory or progressive disease after previous treatment before radiotherapy Kim JY et al Radiat Oncol 8:15, 2013
  24. 24. Kim JY et al Radiat Oncol 8:15, 2013
  25. 25. Kim JY et al Radiat Oncol 8:15, 2013 Med OS 12.9 mo 2YSR 22.2%
  26. 26. Kim JY et al Radiat Oncol 8:15, 2013
  27. 27. • Identification of parameters predicting the deterioration of hepatic function after HT in unresectable LAHCC • Totally 72 patients • Prescription dose : 50 Gy/10fx/2wks (range, 40-60Gy) • RIHT was defined as an increase of at least 2 points in the CP score within 3 months after completion of HT Son SH et al Radiat Oncol 8:11, 2013
  28. 28. 44.4%
  29. 29. Son SH et al Radiat Oncol 8:11, 2013 Cut off value 43.2% Accuracy 0.806(58/72) Sensitivity 0.938 Specificity 0.725
  30. 30. Son SH et al Radiat Oncol 8:11, 2013
  31. 31. Application of our data
  32. 32. • 240 pts with HCC and extrahepatic metastasis (2004-2009) • Local Tx : TACE, RT for intrahepatic tumor • Tx for DM: metastasectomy, RT for metastasis • RT : CFRT, Helical Tomotherapy, cyberknife) • Favorable prognostic factors in multivariate analysis : CP class A, small size tumor, PVTT(-), single metastasis, objective response of intrahepatic tumor after Tx • Leading cause of death : progressive intrahepatic disease • Even in advanced HCC with extrahepatic metastases, intrahepatic control is important in improving patient survival Jung SM et al. J Gastroenterol Hepatol 2012:27;684-9
  33. 33. CR+PR med S 521 days SD+PD med S 170 days (p<0.001) Jung SM et al. J Gastroenterol Hepatol 2012:27;684-9 Survival according to intrahepatic tumor response. Overall survival of 24 patients with objective response was significantly improved, with a median survival of 521 days, as compared to 170 days in the 159 patients without objective tumor response (p<0.001)
  34. 34. • To determine the α/β ratio for normal liver with hepatitis • 98 patients with HCC treated with Helical Tomotherapy were eligible (200603-201202) • Group A (n=66); 45-50Gy in 4.5-5 Gy fractions during 2wks Group B (n=32); 36-60Gy in 2.5-3 Gy fractions during 3-6wks • RIHT was defined as an increase of at least 2 points in CP score within 4 months after completion of Helical Tomotherapy • We attempt to find the statistically significant parameters in the 2 groups using α/β ratio of 2, 4, 6, 8 or 10 and compared the estimated probability curves of each parameter. We hypothesized that the α/β ratio associated with the best matches for the curves between the 2 groups would be equivalent to the α/β ratio for the normal liver with underlying hepatitis Son SH et al Radiat Oncol 8:61, 2013
  35. 35. Summary • Hypofractionated radiotherapy using cyberkinfe or helical tomothrapy was feasible and safe in inoperable hepatocellular carcinma • Even in extrahepatic disease, intrahepatic control may lead the longer survival of patients. Radiotherapy was effective treatment modality to achieve intrahepatic disease control • To predict RIHT defined as an increase at least 2 or more CP score, the a/b ratio should be determined. We’d like to suggest that the a/b ratio is 8, relatively higher value than ever known.
  36. 36. Ongoing investigation • Comparison of treatment outcomes by the difference of f raction size in hypofractionated radiotherapy for the mod erate size of Hepatocelluar Carcinoma (KCCH & CMC) • Significance of an increase in Child-Pugh score after radiotherapy in patients with unresectable hepatocellular carcinoma (CMC)
  37. 37. Thank you for your attention !!

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