CyberKnife can be used to treat liver tumors. It is used to treat liver metastasis, hepatocellular carcinoma and cholangiocarcinoma.

1. Radiosurgery (CyberKnife) in liver tumours:
Indian experience
Debnarayan Dutta
Head, Dept of Radiation Oncology
Amrita Institute of Medical Science, Kochi

2. Liver tumours treated with SBRT
- Liver metastasis
- Hepatocellular carcinoma
- Cholangiocarcinoma

3. Cholangiocarcinoma
- Cholangiocarcinoma: Intrahepatic & hilar region lesion
-Usually small volume disease obstructing CBD & causing jaundice
-Presents with obstructive jaundice
-Majority of the patients have severe malnutrition, compromised liver function
-Usually diagnosed with ERCP and stenting done (mostly metallic)
-Curative treatment is surgery, rarely patients are fit for extensive surgery
-Not responsive to chemotherapy
-Metallic stent gets blocked with tumour & patient die in 3-6 months with jaundice

4. Cholangiocarcinoma

5. Cholangiocarcinoma

6. Cholangiocarcinoma

7. Cholangiocarcinoma

8. Surgery NOT possible:
-Right / left hepatic duct involved
-Peri-portal nodes involved
-Liver metastasis
-Long segment disease
-Poor GC
Surgery NOT possible & non-invasive
focal treatment mandatory
Surgery NOT possible in majority

9. Author Yr n Rec rate Survival
Weimann 1978-96 95 5-Yr 53% 1-Yr 64%
5 Yr 36%
Ohtsuka 1984-2001 48 5 Yr 63% 1-Yr 62%
5 Yr 23%
Jan 1977-97 81 NR 1-Yr 54%
5 Yr 15%
Paik 1994-2005 97 48% 1-Yr 64%
5 Yr 36%
Tan 1988-2003 446 NR 1-Yr 68%
5 Yr 18%
Jonas 1998-2007 195 NR 1-Yr 60%
5 Yr 22%
Zhou 1997-2006 272 NR 1-Yr 58%
5 Yr 26%
Nathan 1988-2004 598 NR 3-Yr 31%
5 Yr 18%
De Jong 1973-2010 449 NR 1-Yr 78%
5 Yr 31%
Luo 2007-2011 1333 NR 1-Yr 58%
5 Yr 17%
Surgery series: Mostly retrospective series
In highly selected cases: 1-Yr OS 60-70% & 5 Yr 20% Simo et al JSO 2016

10. Chemotherapy series: Mostly retrospective series
Author Yr n OS (mo) Survival rate
Kuhlmann 2002-2010 67 11.7 NR
kiefer NR 62 15 1-Yr 61%
3 Yr 8%
Kim 2001-2006 49 10 1-Yr 46%
3 Yr 30%
Novell 1987-1990 57 12.3 NR
Park 2002-2005 43 8.2 NR
Kim 1997-2007 243 7.6 NR
Ray Jr 2005-2012 542 13.4 NR
Hyder 2000-2007 197 13.2 1-Yr 54%
5 Yr 16%
Median Os: 7-12 mo
1-Yr OS 60%
5 Yr 10-20%
Chemotherapy is not promising
Simo et al JSO 2016

11. Author Yr n Rec rate Survival
Madhavan 2006-2014 32 NR 1-Yr 58%
OS 17 mo
Makita 2009-2011 28 NR 1-Yr 59%
Mouli 2003-2011 24 NR NR
Chen 1998-2004 35 NR 1-Yr 92%
3 Yr 52%
Hoffmann 2007-2010 33 NR OS 22 mo
Zeng 1998-2004 38 NR 1-Yr 50%
5 Yr 12%
Radiation therapy series: Mostly retrospective series
In highly selected cases: 1-Yr OS 60-70% &
Dose 45Gy/3#
Need motion management
Majority retrospective series with small patient number
Most studies from Western population & China
Simo et al JSO 2016

12. Radiation therapy: Issues
- Liver moves with respiration at a range of 2-4 cm
- Need motion management
- Liver movement is erratic with respiratory movement
- Need fiducial based ‘real time’ matching- Robotic
radiosurgery system
- Need to deliver high dose
- No or minimal data on radiosurgery in
cholangiocarcinoma

13. Liver tumour movement (n=51 snaps)
Liver movement is more erratic than we think
Snap1 Snap2 Snap3
Lat shift 1.8 1.04 1.2
Ant Shift 1.2 1.28 1.91
Sup shift 2.9 3.3 2.84
Dutta et al AROICON 2012

14. Cholangiocarcinoma: CyberKnife protocol
Liver tumour prior to CK evaluated by hepatic surgeon
Inoperable or not willing for surgery counseled for CK
Assessed with triphasic 320 slice CT scan
Vacloc preparation
MRI scan of liver as per CK protocol
Fiducial placement under USG/CT scan guidance
Wait for 3-5 days for fiducial stabilization
CT scan with vacloc as per CK protocol
Treatment with fiducial tracking on Syncrony
21-45 Gy/3# treatment as per critical structure constraints

15. Planning & treatment execution
Contouring:
CT scan & MRI scan fusion
Occasionally PET scan fusion
Target (GTV) & critical structures contoured
(liver, duodenum, small intestine, kidney)
PTV margin ≅ 2 mm
Planning done: on Multiplan
Plan approved as per:
1.Target coverage
2.Critical structure dose
3.Nodes / beamlets / MU / time
Critical structure constraints as per protocol

16. CK planning: Normal tissue constraints
Organ/ Critical
structure
Dose Constraints
Liver V21<33%
Spinal cord Dmax 22 Gy
Kidney V15< 33%
Stomach V21< 5 cm3
Intestine V16<5 cm3; Dmax < 27 Gy
Duodenum D15 < 5cm3; Dmax < 24 Gy
Timmerman et al, Sem Oncol 2008

17. CK planning

18. Factors n (%)
Age(yr) Mean 62.6.
(44-82)
Gender Male
Female
10(77)
3(23)
Child Pugh A/B
C
12(90)
1(10)
KPS 70-80
90-100
5(40)
8(60)
Hepatitis No
Yes
13(100)
0
Liver status
Normal/fatty liver
Diffuse cirrhosis
12(90)
1(10)
Tumour Vol 114cc
(75-154)
Prior treatment
No treatment
Treatment done
TACE
Progression
Non responsive
Metallic stenting done
6(46)
7(54)
0
6(46)
1(10)
12(90)
Demography (n=19)

19. Serum bilirubin parameters (n=8)SerumBilirubin
Majority of the patients had >6 months jaundice free period

20. Dosimetric parameters (n=19)
Parameters
45Gy/3# 6 (40)
39Gy/3# 6 (40)
21Gy/3# 3 (30)
Max dose (Gy) 38.7 (23.5-51)
CI 1.1 (0.92-1.33)
nCI 1.28 (1.16-1.38)
HI 1.19 (1.18-1.25)
Coverage 96.6 (95-100)
Prescription Iso (%) 89% (80-100)
GTV vol 114cc (75-154)
Mean liver dose 6Gy
Mean SI dose 10 Gy
2% SI vol dose 2 Gy

21. month
Mean OS (mo) 9.6
SD (mo) 11.4
(0.7-35)
Status at LFU
Stable
Local progression
Metastasis*
Dead^
Alive
5 (40)
4 (30)
4(30)
6 (45)
7 (55)
GI Toxicity Gr- I-II 4 (30)
Post-CK Rx
Chemotherapy 5(30)
Outcome & toxicity (n=19)
Median Follow up 10 months (1-35 mo)
Median survival: 9.6 months
Jaundice free Survival > 6 months: 10 pt (80)

22. Survival function
Mean Survival 9.6 mo
Range 0.7-35 mo
SD 11.4 mo
6/19 (33%) pts surviving > 1 yr
2-yr Actuarial survival 20%
2/19 (10%) pt > 3 yrs

23. Case#1
July 2013
72/M
Cholangio Ca
Post stenting
Post-CK July 2013
21Gy/3#
Initial Bilirubin 16 gm/dl
Post stenting

24. Case#1
March 2014
2014: Post CK good response
Bilirubin- 0.8mg/dl
GC- good
KPS 90

25. Case#1
March 2015
Metastasis in liver
Re-CK done 45Gy/3#
Bilirubin – Normal
On Chemotherapy
Expired on Dec 2015
Survival 30 months

26. Follow up: Metastasis to liver

27. Fiducial placement: issues & promises
Is it possible to track metallic stent with ‘lung volume’ tracking algorithm

28. •
Cholangiocarcinoma patients usually have metallic stent in place
•
Metallic stent is visible in 6D X-ray tracking system
-
Issues are-
-
1) ‘density’ or specific ‘Houndsfield’ necessary for optimal tracking may not be sufficient
-
2) As ‘stent’ is a moving structure with respiration, need to track the metallic stent on
synchrony. Need to evaluate the effectiveness of Synchrony’ system in this scenario;
-
3) Stent is not a ‘dot’ like structure (fiducial like) but like tumour in lung (elongated), need
to use lung tracking algorithm,
-
4) Efficacy & possibility of ‘lung tracking’ algorithm need to be evaluated for tracking
metallic stent
-
5) If possible to track the metallic stent accurately, hazards of fiducial placement
process may be avoided
-
Tracking of metallic stent

29. 
Fiducial was trackable with synchrony

Fiducial was representing the tracking with Synchrony

Metallic stent representing the tracking volume (tumour)

Correlation with fiducial movement with respiration was not correlating with
metallic stent movement with respiration [Fig 3&4]

Hence, fiducial was not ‘suitable’ for tracking of the tumour
Tracking fiducial with Synchrony for treatment:
Anjali Menon, YROC 2017

30. 
- Metallic stent was trackable with 6D X-ray with revised acquisition parameters (Volt , MA )

- Differential image acquisition parameters for both side X-rays required for optimal image

- Metallic stent representing tracking volume (tumour), hence higher representation of tumour

- Metallic stent though trackable, rotational error was significant and was not corresponding

with respiratory movement

- Metallic stent with 6D X-ray is trackable but NOT suitable for treatment execution
Tracking metallic stent with 6D X-ray
Anjali Menon, YROC 2017

31. 
Metallic stent was trackable with 6D X-ray with revised imaging acquisition parameters
(Voltage , MA )

Tracking of stent with X-sight lung protocol done on Synchrony for assessment of suitability

Differential image acquisition parameters for both side X-rays required for optimal image

Metallic stent with X-sight lung on Synchrony tracking method is trackable

Tracking in different coordinates are within limits
Tracking metallic stent with Xsight lung:
Anjali Menon, YROC 2017

32. Correlation Error: Metallic stent with Xsight lung [On Treatment setup day]:
Xsight Lung for Stent Tracking: A novel utility for Xsight Lung tumour tracking system
Tracking metallic stent with Xsight lung (simulation day)
Anjali Menon, YROC 2017

33. •
Correlation with metallic stent movement with respiration was not reproducible during
treatment process
•
1) Fatigue, 2) fullness of bowel (stomach), 3) peristaltic movement influence the
movement of stent, difficult to re-produce the similar pattern in repeated treatment
sittings
Correlation Error: Metallic stent with Xsight lung [On Rx execution day]
CONCLUSIONS: 1. Tracking metallic stent was feasible but poor correlation.
2. Hence not suitable for tracking in multiple sittings
Anjali Menon, YROC 2017

34. Cholangiocarcinoma: take HOME
- There is emerging role of SBRT in cholangiocarcinoma
- ‘Jaundice free’ survival is high after SBRT
- With SBRT, local control is high
- However, there is no significant improvement in overall survival
- Because, metastasis to liver & other viscera compromising Survival
- NEED efficient systemic therapy along with SBRT to improve survival

35. Sonaki N et al, W J Gastro 2015
HCC Management
Role of Radiosurgery in HCC is established

36. CLOCC study
Presented By Theo Ruers at 2015 ASCO Annual Meeting ASC0 2015 Abstr

37. Overall Survival
Presented By Theo Ruers at 2015 ASCO Annual Meeting ASC0 2015 Abstr

38. Demographic profile (n=65)
49 patients with 65 lesions
Mean age: 57.5 yrs
Male: 82%
Child Pugh A & B: 64%
KPS>80: 24%
Hepatitis: 46%
Single lesion: 72%
Tumour vol <90cc: 66%
Prior Rx: 76%
Initial data published
Dutta et al ESTRO 2013 (Abstr)

39. All pt HCC Mets
PTV (Target)
Mean vol (cc)
Range (cc)
Max dose (Gy)
Mean dose (Gy)
Prescription isodose (%)
Target Coverage (%)
Mean CI
Mean nCI
Mean HI
192
(10-
710)
36.3
33.3
84
94
1.13
1.28
1.19
196
(10-
710)
39
35.7
84
94
1.06
1.26
1.18
200
(50.7-628)
36
33.5
84
92
1.21
1.31
1.19
Liver
Mean volume (cc)
Mean dose (Gy)
20Gy Vol (cc)
10Gy Vol (cc)
800cc liver dose (Gy)
1197
4.7
111
357
8.2
1143
4.3
92.9
313.7
7.5
1582
7
182.5
532
10.2
Small intestine
Mean dose (Gy)
2% volume dose (Gy)
3.4
10.6
2.8
8.9
3.2
9.9
Dosimetry
Mean target Vol: 192 cc
Pres Isodose: 84%
Target coverage: 94%
Mean dose: 33 Gy
Dose Range: 21-45Gy
Fractions: 3
Mean liver dose: 4.7 Gy
800 cc liver: < 8.2 Gy
2% Small Intestine: 10.6 Gy

40. Survival function
p-value: NS
Median Survival:
HCC: 10.1 mo
Mets: 9.0 mo
1yr Survival:
HCC: 45%
Mets: 30%
Dutta et al ESTRO 2013 (Abstr)

41. Factors Median OS
(mo)
p-value^
KPS
70-80 8.3
0.034
90-100 15.4
Child Pugh
A/B 13.3
0.039
C 4.9
Cirrhosis
No 13.3
0.005
Yes 9.4
Prior Rx
yes 8.3
0.006
No 16.6
Hepatitis
No 10.5
0.977
yes 9.5
Dose
<39Gy 9.5
0.02
>39Gy 15.4
Volume
<10cc 15.7
0.011
>90cc 7.2
Factors influence outcome
1) Higher KPS,
2) Favourable Child Pugh,
3) No corrhosis,
4) No prior Rx,
5) Dose>39Gy
6) Small volume disease patients
have significantly better survival
^Log Rank test

42. Our Survival function data: HCC
Study Type n Survival (mo) Toxicity (Gr-3/4)
Llovet JM* (2008) Ph III 602 10.7
Abou-Alfa GK^ (2006) Ph II 137 9.2 Fatigue (5%),
diarrhea (8.0%),
hand-foot dis (5.1%)
Cheng AL (2009) Ph III 271 6.5
Our study (2015) Retro 65 10.4 1 pt with anecteric
hepatitis
Our pt cohort is heavily pre-treated (76%),
Progression on chemotherapy
and high viral load (Hep B/C)

43. Challenges: evaluation for local control
NO suitable imaging method to assess response after CK,
need to evaluate efficacy only with Survival Function

46. Case#1: Ca Breast with solitary liver mets
48/F; Diagnosed with breast lump (L) in 2011
FNAC- IDC gr III
PET Scan- 2x2 cm mass in liver
2x2 cm mass in L breast
FNAC from liver mass- IDC
Stage- T1NoM1 (Stage IV)
MRM done
SBRT for liver nodule- 45Gy/3# 2011
ER/PR+ve, Her2neu 3+
Chemotherapy/ Herceptin
Hormone therapy
2016: CR
On Hormone therapy

47. Case#2: Liver ONLY disease with recurrences
35/F; Diagnosed with breast lump (R) in 2010
FNAC- IDC gr III
2010:
BCS done 2010
Chemotherapy
2014:
Multiple liver mets
Chemotherapy
Not responding / progressing on CT
Oct 2015: PD-1 blocker (Iprulimab)
SBRT- 3 lesions (>2.5 cm)
Mar 2016: Untreated lesions disappeared
No active disease
Oct, 2016:
New single lesion in liver- planned for re-treatment

48. Conclusions
- There is emerging role of SBRT in liver tumours
- Liver metastasis- Oligo metastasis
- HCC- radical intent, recurrent setting, ‘bridge to transplant’
- Cholangiocarcinoma- as radical treatment in inoperable