BRIEF ABOUT MANGEMENT OF HEPATOCELLULAR CARCINOMA ALONG WITH ROLE OF SBRT AND ITS BRIDING FOR LT.

1. MANGEMENT OF
HCC
By-DR ANUKUL DUTTA
DR SURYAPRAKASH(Moderator)

2. TOPICS
1 –Incidence
2-Biological markers
3-Staging evaluation
4-Primary/curative Treatment
5-Loco regional Treatment
6-Locally Advanced Disease and
palliation.

3. HCC-INCIDENCE AS PER GLOBOCON 2020

5. BIOLOGICAL CHARCATERSTICS
• HBV Infection , Inactive HBV infection , HCV infection and cirrhosis are strongly associated
with the development of HCC
• Obesity ,Diabetes, Alcohol ,OCPS are also associated with the development of HCC.
• HBV viral DNA are frequently found within the genome of the HCC, in patient with HBV
infection and HBV cirrhosis , Interferon therapy reduces the risk of developing HCC and
increase survival
• However limited studies/evidence suggesting benefit of interferon therapy in HCV
infection or HCV cirrhosis.

6. Molecular biology
Integration of viral DNA is
necessary for
carcinogenesis
Mechanism
Genomic instability from
deletions and chromosomal
rearrangement rather than
specific oncogene
activation or disruption of
tumour suppression genes.
Hepato-carcinogenesis
VARIOUS PATHWAY
*vascular endothelial
growth factor (VEGF)
*epidermal growth factor
(EGF)
*hepatocyte growth factor
(HCF)
*Insulin like growth factor
(ICF) ,

7. Molecular biology
ALL THE ABOVEMENTIONED
PATHWAY ACTIVATES -
SIGNAL TRANSDUCTION VIA
THE RAS/MAPK PATHWAY
ACTIVATION OF THE
RAS/MAPK PATHWAY LEADS
TO HCC GROWTH AND
PROLIFERATION
TYROSINE KINASE
INHIBITORS(BLOCKS THESE
PATHWAY)
SORAFENIB ,
ATELOZOLIZUMAB
,BEVACIZUMAB.

8. CLINICAL
MANIFESTATION
AND STAGING.
• SYMPTOMS-
• HCC MOST FREQUENTLY PRESENT WITH RIGHT
UPPER ABDOMINAL PAIN , EPIGASTRIC OR
DISCOMFORT.
• THE PAIN IS USUALLY DULL ACHE IN NATURE ,
RARELY PATIENT PRESENTS WITH SHARP PAIN.
• PATIENT MAY ALSO PRESENT WITH SUDDEN ,SEVERE
PAIN RELATED TO AN ACUTE HCC RUPTURE AND
BLEED.
• SIGNS-
• MOST COMMON FINDING IN PATIENT WITH
PRIMARY HEPATIC TUMOR IS HEPATOMEGALY ,
VARIATION MAY BE SEEN AS FIBROTIC SHRINKAGE
FOUND IN CIRRHOSIS.

9. LABORATORY
STUDIES
• LAB WORKUP OF PATIENT IS TO DEFINE/ ASSESS
LIVER FUNCTION.
• CBC, LFT (ALBUMIN, BILIRUBIN AND
COAGULATION STUDIES )
• SERUM AFP IS WIDELY USED TUMOR MARKER
(normal range -10-20microgram/litre)
Greater than 400 microgram/litre suggestive of
HCC (not diagnostic)
*AFP levels are particularly useful in monitoring
treated patients for recurrence after
normalization of levels.
*HCC outcomes with high viral loads associated
with worse survival.

10. RADIOLOGICAL STUDIES
• TRIPHASIC COMPUTED TOMOGRAPHY (CT)
• MRI
• Above modalities asses vascularity , extent of tumour , vascular invasion
and for diagnosis.
• HCC is hyper vascular and typically displays arterial enhancement with
washout in venous and delayed phases with capsule Enhancement.

12. RADIOLOGICAL STUDIES
• MRI should be the liver imaging modality of choice in patient with cirrhosis in view of superior
contrast resolution.
• LIVER IMAGING REPORTING AND DATA SYSTEM (LI-RADS) by American college of radiology.
• It is used to estimate the likelihood of HCC in patients with a lesion found in the background of
a cirrhotic liver.
• Lesions are classified by imaging characteristics (size, interval growth, enhancement, washout,
and capsule) in a range between LI-RADS 1 (benign) and LI-RADS 5 (definitely HCC).
• The designation of LI-RADS 5 is considered to be unequivocal and sufficient to render a
diagnosis of HCC without a biopsy.

13. RADIOLOGICAL STUDIES
• CT of the chest, abdomen, and pelvis is recommended to rule out
extrahepatic spread; bone scan can be considered if clinically indicated.
• Positron emission tomography (PET)/CT has been used to evaluate
extrahepatic metastases; however, it is not as sensitive as multiphasic liver
CT or MR for evaluating the hepatic extent of tumor.

14. TNM STAGING

15. CHILD PUGH
SCORE

16. BCLC(Barcelona clinic liver cancer staging)

17. PRIMARY TREATMENT
• SURGERY-RESECTION/ ORTHOTOPIC LIVER TRANSPLANTION
• BLCL STAGE 0
• PS ZERO +CHILD PUGH A
• TUMOR SIZE <2 CM- SINGLE OR FAVORABLE MULTIFOCAL TUMOR
• SUFFICIENT LIVER RESERVE AND NORMAL PORTAL PRESSURE ----
PARTIAL HEPATECTOMY

18. PRIMARY TREATMENT
• BLCL STAGE A
• PS 0 + CHILD PUGH A/B
• SINGLE TUMOR < 5CM
• UPTO 3 TUMORS ALL<3CM
• SUFFICIENT LIVER RESERVE AND NORMAL PORTAL PRESSURE—
PARTIAL HEPATECTOMY
• INSUFFICENT LIVER RESERVE AND/OR ELEVATED PORTAL PRESURRE –
LIVER TRANSPLANT.

19. Milan liver
transplantation.

20. Locoregional therapy
• RADIOFREQUENCY ABLATION
• MICROWAVE ABLATION
• SBRT
• SIRT (SELECTIVE INTERNAL RADIOTHERAPY).

21. Locoregional therapy
• BLCL STAGE B
• PS-O + CHILD PUGH A/B
• MULTIPLE TUMORS
• A] NUMBER OF TUMOR<3 WITH SIZE LESS THAN 1-2 CM
*RFA/MWA
*SBRT
*SIRT

22. Radiofrequency
ablation

23. Locoregional therapy
• BLCL STAGE B
• PS-O + CHILD PUGH A/B
• MULTIPLE TUMORS
• B]N0 OF TUMOR <3 WITH 2-5CM
• *SBRT
• *RFA/MWA
• *SIRT

24. Locoregional therapy
• BLCL STAGE B
• PS-O + CHILD PUGH A/B
• MULTIPLE TUMORS
• C]NO OF TUMOR <3 WITH SIZE MORE THAN 5 CM
• *TACE TRANSARTERIAL CHEMO- EMBLOIZATION
• *SIRT
• # FOR ALL BLCL STAGE B POST TREATMENT –
OBSERVATION FOR LOCAL RECURRENCE /INCREASE IN
BIOLOGICAL MARKERS

26. Locoregional therapy
• BLCL STAGE C
• PS 1-2
• CHILD PUGH A/B
• PORTAL INVASION
• LYMPH NODE INV OR M1 DISEASE
A]ONLY PORTAL INVASION FAVOURABLE DISEASE – SBRT/TACE /SIRT
B]LYMPH NODE OR M1 DISEASE – SYSTEMIC THERAPY (SORAFENIB VS
ATEZOLIZUMAB+BEVACIZUMAB)

27. Locoregional therapy
• STAGE D
• PS 3-4
• CHILD PUGH C
• PALLATIVE RT FOR SYMPTOMIC LESION
• BEST SUPPORTIVE CARE

28. SBRT(STEREOTATIC BODY RADIATION THERAPY)
• Méndez Romero et al. obtained local control (LC) in six out of eight HCC
patients after applying two different dose fractionation schedules:
• A] 37.5 Gy in three fractions and 25 Gy in five fractions .
• Two episodes of Radiation-Induced Liver Disease (RILD) and one death due
to hepatic failure was observed.
• No late toxicity was found

29. SBRT(STEREOTATIC BODY RADIATION THERAPY
• Tse et al. included 41 patients with relatively large unresectable tumors .
• SBRT (median dose of 36 Gy in six fractions)
• The median survival time was 13.4 months with 1-year infield LC rates of
65%.
• Within the first 3 months after treatment, no RILD or treatment-related
death was noted.
• The promising results from previous trials established the ground for
further phase II studies of three to six-fraction SBRT.

30. SBRT as a Bridge to Transplant
• Although SBRT is a local therapy most frequently used for patients
unsuitable for surgery
• It can also be used as a bridge procedure to downstage lesions that do not
meet the Milan for LT or to prevent tumor progression while patients are
on a waiting list for LT.
• In 2011 O’Connor et al. evaluated a series of 10 patients with 11 HCC
lesions treated with SBRT while on the LT waiting list. Local control over
this period was 100% and all patients underwent LT without increased
surgical complications.

31. SUMMARY

32. • THANK YOU.