clinical experiences of ck/ht in hepatocellular carcinoma

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 HospitalThe Catholic University of Korea

Contents

• The treatment outcome after CK

• The treatment outcome after HT

• The application of our data in HCC

• Ongoing investigation

Experience of CK in CMC

• Retrospective study to evaluate the efficacy of SBRT for small non-re-

sectable 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

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

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%


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 dis-

ease in 1-2 months after SBRT

3. No progression from CP class B af-

ter SBRT

4. No hematologic toxicity over grade

2 was found.

5. No grade 3 or greater GI toxicity in-

cluding nausea was found.

Choi et al BMC cancer 8:351, 2008

• 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


• Flow of study participant in the study

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 repre-sents 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


• Pattern of disease recurrenceCR; complete responsePD; progressive disease

28.6%

Intrahepatic PD; 59.5%

Son SH et al. Int J Radiat Oncol Biol Phys. 2010:78;1073-1080

• Identification of the parameters to predict hepatic toxicity and dete-

rioration 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)

Son SH et al. Int J Radiat Oncol Biol Phys. 2010:78;1073-1080

AUC 0.997P = 0.002

Experiences of HT in CMC

Jang JW et al. Int J Radiat Oncol Biol Phys. 2009:74;412-8

50 Gy/10 fractions/2 weeks

• 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 metas-

tases, 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%


6 months

12 months

18 months

24 months Median

OSR 75.2% 50.1% 19.9% 14.9% 12.3 months

OPFS 42.7% 9.6% 10.5 months

IPFS 79.0% 61.5%

Helical Tomotherapy is safe and feasible without major toxici-ties for the treatment of advanced HCC and results in excellent local control and a potential survival benefit.


Kim JY et al Radiat Oncol 8:15, 2013

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



Med OS 12.9 mo2YSR 22.2%

• 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


Cut off value 43.2%Accuracy 0.806(58/72)Sensitivity 0.938Specificity 0.725

Application of our data

• 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

CR+PR med S 521 daysSD+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 re-sponse (p<0.001)

• 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 hep-

atitis


Summary • Hypofractionated radiotherapy using cyberkinfe

or helical tomothrapy was feasible and safe in in-operable hepatocellular carcinma

• Even in extrahepatic disease, intrahepatic control may lead the longer survival of patients. Radio-therapy 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 deter-mined. We’d like to suggest that the a/b ratio is 8, relatively higher value than ever known.

Ongoing investigation

• Comparison of treatment outcomes by the differ-ence of fraction size in hypofractionated radio-therapy for the moderate size of Hepatocelluar Carcinoma (KCCH & CMC)

• Significance of an increase in Child-Pugh score af-ter radiotherapy in patients with unresectable hepatocellular carcinoma (CMC)

Thank you for your attention !!

clinical experiences of ck/ht in hepatocellular carcinoma

Health & Medicine

hcc patients

months range

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choi et

bmc cancer

months kwon jh et

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hcc lesions

￼clinical experiences of ck/ht in hepatocellular carcinoma

clinical experiences of ck/ht in hepatocellular carcinoma