1. Aintree University Hospital
Liverpool, UK
Irinotecan Loaded DC Beads as Neoadjuvant Treatment of Resectable Colorectal Liver Metastases
Stephen W Fenwick MD FRCS
Consultant Hepatobiliary Surgeon
Belfast, September 2011

2. Plan Systemic chemotherapy in CRLM Targeted chemotherapy
Phase II trial of targeted chemotherapy in resectable colorectal metastases (Paragon II study)
Declaration
Stephen Fenwick is a consultant to Biocompatibles UK LTD.

3. Five-year survival of English colorectal cancer patients1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
All stage 4 resected n=3116
All patients
Survival probability
All stage 3
All Stage 4
0.5 1
1.5 2
2.5 3
3.5 4
4.5 5
Years
Patients with resected liver metastases
All patients without resected metastases
Dukes C
Dukes D
Morris EJA et al. Brit J Surg 2010; 97: 3

4. Survival after liver resection for colorectal liver metastases
Not due to
selection bias
Survival stratified by year
of surgery (1997–2005)
1.0
0.8
1997
1998
1999
2000
2001
2002
2003
2004
2005
1997-censored
1998-censored
2000-censored
2001-censored
2002-censored
2003-censored
2004-censored
2005-censored
0.6
Cumulative Survival
0.4
So why are we
getting better?
0.2
0.0
1000
2000
3000
4000
Survival Time 4

5. EPOC study
Lancet 2008; 371: 5

6. Study design N=364 patients Randomize FOLFOX4 Surgery FOLFOX4 Surgery
6 cycles
(3 months)
6 cycles
(3 months)
Surgery
N=364 patients
Nordlinger et al. Lancet 2008; 371: 6

7. Progression-free survival in resected patients
100
HR= 0.73; CI: , p=0.025 90 80
Periop CT
+9.2% At 3 years 70 60 50
42.4% 40
Surgery only 30
33.2% 20 10
(years) 1 2 3 4 5 6 O N
Number of patients at risk :
104
152 85 59 39 24 10 93
151
118 76 45 23 6
Nordlinger et al. Lancet 2008; 371: 7

8. Correlation of outcome after hepatectomy to histologic response to neoadjuvant chemotherapy
Blazer et al.
2008; 26:
Complete
response
Major
response
Minor
response

9. Secondary liver resection rates of metastases and tumour response
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0.7
0.8
0.9
Resection rate
Response rate
Studies including selected liver metastases only patients (no extrahepatic disease)
(r=0.96; p=0.002)
Response rates >70%
in unresectable liver
only patients equates
>40% liver resection
rate
Studies including non-selected patients with mCRC
(solid line)
(r=0.74; p<0.001)
Phase III studies including
non-selected patients with mCRC
(dashed line)
(r=0.67; p=0.024)
Folprecht G, et al. Ann Oncol 2005;16:1311–1319 9

10. How to bring more patients to resection?
Downstage the disease to make it resectable
And / Or
“Upstage” the surgical techniques

11. What are the problems with pre-operative chemotherapy ?

12. Oxaliplatin Irinotecan
Chemotherapy liver damage
Oxaliplatin Irinotecan
Sinusoidal Obstruction
Syndrome
Increased peri-operative
bleeding
Steatohepatitis
Increased post
operative liver
failure & 90 day
mortality
‘Blue’ liver
‘Yellow’ liver

13. Complications of surgery
Peri-op CT
Surgery
Post-operative complications*
40 /159 (25.2%)
27 / 170 (15.9%)
Cardio-pulmonary failure 3 2
Bleeding
Biliary Fistula 12 5
(Incl Output > 100ml/d, >10d)
(9)
(2)
Hepatic Failure 11 8
(Incl. Bilirubin>10mg/dl, >3d)
(10)
(5)
Wound infection 4
Intra-abdominal infection
Need for reoperation
Other 25 16
Incl. post-operative death
1 patient
2 patients
EPOC Study (EORTC 40983) *
Nordlinger et al. Lancet 2008; 371:
*P=0.04 13

14. "Complete response" : does it mean cure ?
Wait for it to
come back? ?
Before treatment
After 6 cycles of chemotherapy 14

15. Dangerous Halo Macroscopic CR after chemotherapy:
~20% of cells in periphery are viable
Dangerous
Halo
Courtesy of Professors G Mentha and L Rubbia Brandt, University of Geneva

16. Too much pre-surgery chemotherapy
Problems for the liver surgeon
Excessive Oxaliplatin
Excessive bleeding at surgery
Excessive Irinotecan
Increased risk of post operative liver failure and 90 day mortality
Complete response
“Disappearing” tumours

17. Targeted chemotherapy?17

18. Single administration, so reduced hepatic and systemic toxicity?
What would be the advantages of DC bead TACE over conventional therapy?
Single administration, so reduced hepatic and systemic toxicity?
Targeted, so protecting ‘normal’ liver?
Could be combined with metal filings to radio-locate disappearing lesions?
Cheaper?
Faster action, so possibly shorter delay from treatment to surgery? 18

19. Trial proposal
Study to evaluate safety/toxicity of targeted neoadjuvant irinotecan DC beads in patients with resectable colorectal liver metastases
PARAGON II STUDY 19

20. Study Design Multicentre, open label, single arm phase II study
Primary endpoint – tumour resectability at surgery (% with R0 resection)
Secondary endpoints
Adverse events
Radiological response
Pathological response
Survival
Competitive studies:
UK: New EPOC
EORTC 40051: BOS

21. Participating Centres
Liverpool
Basingstoke
Paris (Villejuif)
Girona
Vienna
Pathology review at a single centre

22. Paragon II Trial Design
40 patients with easily resectable colorectal liver metastases
One TACE using Irinotecan loaded beads
Liver resection 4 weeks later

23. Paragon II Trial Design
micron Paragon beads, loaded with irinotecan during manufacture
Aim to give 200mg
Selective embolisation to stasis

24. Inclusion Criteria 18-80 yrs, not pregnant or lactating
Potentially resectable disease, confined to liver
Unilobar disease, <4 lesions
No chemotherapy up to 1 month previously
No other primary cancer within past 10 yrs
Not enrolled in another trial within 30 days
Adequate liver, and bone marrow function
WCC>3, Platelets >100, Bilirubin<1.5x normal
Prothrombin time not more than>50% of normal

25. Inclusion Criteria 18-80 yrs, not pregnant or lactating
Potentially resectable disease, confined to liver
Unilobar disease, <4 lesions
No chemotherapy up to 1 month previously
No other primary cancer within past 10 yrs
Not enrolled in another trial within 30 days
Adequate liver, and bone marrow function
WCC>3, Platelets >100, Bilirubin<1.5x normal
Prothrombin time not more than>50% of normal

26. Exclusion Criteria Extra-hepatic disease
Contraindications to Irinotecan
Active infection
Allergy to Contrast media
Contraindications to Hepatic Artery embolisation
Severe atherosclerosis

27. Trial Schedule Baseline (PET)CT within 1 month of procedure TACE
4 weeks
CT followed by liver resection
Follow up CT at 3, 6, 9 & 12 months.

28. Technical considerations
PARAGON beads are easy to use
4 hour “life”
Small tumours more difficulty to localise
Contrast enhanced US
C arm CT

29. Post embolization Pain and nausea expected Pre procedure NSAIDs
Manage with IV anti-emetics at time of embolisation
Post procedure IV Narcotics, Morphine via PCA, IV paracetemol, NSAIDs, and occasionally Entonox
Intra arterial lidocaine

30. Recruitment Recruitment so far Centre Recruited Embolized Laparotomy 1
39 patients 26/08/2011
1st patient 11/02/2009
1.3 patients/month
Recruitment so far
Centre
Recruited
Embolized
Laparotomy
Basingstoke 1
Girona 3
Liverpool 26 25
Paris
Vienna 8

31. Recruitment Included Patients (n = 48, intention to treat population)
Ineligible for TACE after inclusion (n = 9)
Patients treated with TACE (n = 39)
Ineligible for resection after TACE (n = 2)
Patients treated with surgery (n = 36, one patient is waiting for surgery)
Patient JMP (TACE 14/05/10, Surgery 17/08/10) had a follow-up scan 19/07/2011 that showed no recurrence, we should therefore be at 19 patients followed up for a year, however, K-H (TACE 24/03/10, Surgery 27/04/10) has had his “12 month” scan delayed until 15/09/2011, 9 month scan not done, no recurrence was last confirmed at 6 month scan 16/09/ The final status of patient JAB has not been confirmed (has been requested).
Withdrawn from the set of patients that had been followed for 12 months in total 8/18 (44%)
Withdrawn for progressive disease 5/18 (28%). In addition, 1 patient presented with progression at 12 months, total with progressive disease 6/18 (33%)
Three of the 18 patients were not eligible for the per protocol population: two patients tragically died, one patient had HCC, and had been misdiagnosed with liver metastases, the PFS population was therefore 15 patients (at the end of April 2011).
After April 2010 the radiology suite at the top recruiting centre at Aintree was rebuilt, and a 5 month gap in recruitment ensued. Meetings to stress the importance of continued recruitment were held with Investigators, and two new sites (Vienna and Manchester) were involved.
Recruitment picked up from October 2010, since then 18 patients have been included (2.3 patients/month), 2 of these patients did not receive TACE, 2 patients were excluded after TACE for peritoneal carcinomatosis, and one patient ( E-W) was withdrawn because of disease progression.
By the end of December this year an additional 7 patients will be completing their 12 month follow up, 2 of these 7 have so far been withdrawn, 1 due to peritoneal carcinomatosis discovered at surgery (not considered disease progression while in the study, but considered previously unknown advanced disease discovered during surgery, not included in the PFS population) and one ( E-W) due to recurrence [to be updated: the PFS population by the end of December 2012 will be 21, 7/21 (33%) have progressed, one year PFS = 67%].
Withdrawn after surgery (n = 11)
12 months follow-up (n = 18) 31

32. Patients excluded before TACE
Bilobar metastases (2)
Withdrew consent (2)
Pulmonary metastases
Suspected HCC
Allergy to contrast
Unable to canulate segmental artery
Tumour vessels not seen at angiography

33. Patients excluded before resection
Peritoneal disease at laparotomy

34. Paragon II Patient characteristics
n = 48, 10 female (21%), 38 male (79%)
Age ±SD at TACE visit: 62 ±11 years (range 36-78)
1-3 tumours at screening, average 1.33
1-4 tumours prior to TACE, average 1.4
Longest diameter pre TACE 44 mm (range 9-100)
The sex ratio in this study is different from but close to the one expected in a random patient population. Although the overall lifetime risk for the development of colorectal carcinoma is similar in both sexes, male patients comprise 62% of all patients undergoing hepatectomy in the UK and females 38% (Morris et al. 2010). Sex significantly influences the clinical and pathological characteristics of colorectal cancer, including survival, histopathology and microsatellite status (Koo et al. 2010). We might want to consider stratification for equal sex ratios in future randomised studies.
The age in the included patient population was 61.9±11.2 years, with a range of years (the confirmed age was not available for two of the patients).
Patient J-W had ECOG status 1 at screening (this patient was excluded before TACE because of a second lesion suspected to be an HCC tumour seen on the pre TACE scan).
The Chief Investigator wanted to include easily resectable patients, the average number of tumours being 1.4 and the sum longest diameter being 44 mm is in correspondence with this. The Investigators have eventually also included some patients with more extensive tumours, if we want to avoid these in the future we could consider an exclusion criterion on sum longest diameter. Interestingly, the Nordlinger et al. (2008) study had an average sum largest diameter virtually the same as this, 50 mm, but with a range higher in the spectrum ( mm).
References
Koo JH, Leong RW. Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer. J Gastroenterol Hepatol Jan;25(1): Epub 2009 Oct 27.
Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, Cottier B, Poston G. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg Jul;97(7):
Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet Mar 22;371(9617): 34

35. Withdrawn During 12M Follow-up
B-L Progressive disease (new lesions, p.hepatis, lung nodules)
W-W Progressive disease (new lesion)
JOD Progressive disease (new lesions)
JHO Progressive at 12 months (target+non-trgt)
V-L Progressive disease (new lesion)
AMR Diagnosed as HCC by histology
RAA Unrelated death (pneumomediastinum)
C-G Progressive disease (new lesions)
G-W Unrelated death (aspiration, organ failure)
JAB Outcome after 12 months to be confirmed
The 6 disease progressions I have had confirmed so far, in summary:
B-L Original tumour in segment 8, later progression (first seen on CT scan 19/12/2009): at the porta hepatis, some retroperitoneal nodes and bilateral pulmonary metastases, while the liver appeared clear B-L The patient had a recurrence including new hepatic lesion (i.e. not recurrence) plus multiple nodules in the lung. Withdrew to have palliative chemotherapy at a hospital closer to his home (he lived quite a distance away from Aintree).
W-W Original tumour in segment 6, later progression: 2 new lesions in segments 4b and 8.
JOD Original tumour in segment 8, later progression: no recurrence of target lesions, two new lesions, one in segment 2 and one in segment 5, no new extrahepatic lesions. Patient withdrew on study visit 31/12/2009, but the new hepatic lesions were seen on scan from 29/12/2009.
V-L Original tumours: one in segment 6 and one in segment 7, these were treated with TACE. During surgery a third tumour found in segment 2 (not treated with TACE). Later progression in the caudate lobe (segment 1) i.e. new hepatic lesion, no recurrence of resected lesions. Possible extrahepatic progression, this needs to be confirmed by the Surgeon (Hassan Malik).
C-G Original tumours: one in segment 4b. The CT report 27/05/2010 notes that the non specific linear and patchy low attenuation changes in segment 6 should be kept under further surveillance, but that there is no definite evidence of residual disease or recurrence. The CT report addendum (referring to examination date 07/10/2010) says there is evidence of two liver metastases at the junction of segment 6/7 and another in segment 4a. No local recurrence at the site of previous resection around segment 4b and 5. The date of progression should be 24/09/2010, the PET-CT on this date reported “multiple metastatic deposits in both lobes. In addition …” the conclusion was that there were several metastases in new locations in the liver, and positive upper abdominal nodes (i.e. extrahepatic disease).
JHO Original tumours: one in segment 2 and one in segment 3, later progression: hepatic and extrahepatic recurrence, one lesion in segment 7 and possibly at the resection margin, extrahepatic lesions in the right lung; in the right para thraceal aspect and in the sub carinal region; in the presacral aspect.
Right now, we are able to say something about progression-free 12 month follow-up for all patients up to JMP (TACE 14/05/2010). The next patient had TACE 08/10/2010 (this was the 5 month gap in recruitment last year while the Radiology Department at Aintree was rebuilt) , so further data will be available starting in October 2011 (an additional 6 patients by December 2011).
Up until JMP 19 patients had TACE (14 at Aintree, 1 in Basingstoke, 4 in Spain). One patient was excluded after surgery because histology confirmed the patient’s disease as HCC, this patient has been excluded from the group of patients (I think this makes sense. If I am mistaken our preliminary data would look even better), so I am comparing with 18 patients.
In total 8/18 patients (44%) were withdrawn (I include the HCC patient in the description of the withdrawal group, to report this important category of withdrawal, one other patient was withdrawn before TACE because of suspected HCC concomitant with the liver metastasis).
B-L Was withdrawn because of a new hepatic malignancy (his original tumour was in segment VIII, i.e. TACE in right lobe, around the time of the 9M visit the CT showed malignant lymphadenopathy at the porta hepatis leading to bile duct obstruction. The patient was admitted to general ward 21/12/2009 with the diagnosis of obstructive jaundice due to recurrent colorectal cancer. The CT scan also showed some retroperitoneal nodes and bilateral pulmonary metastases, while the liver appeared clear.)
JOD Withdrew at the 9M F-U visit. No recurrence of target lesions, two new hepatic lesions, one in segment II and one in segment V (original tumour was in segment VIII), no new extrahepatic lesions.
In addition to the patients withdrawn during the 12 month follow-up period, patient JHO had hepatic and extrahepatic recurrence identified on the CT scan performed 13/07/2010, close to 12 months after her TACE procedure 24/07/ On this scan she had one pulmonary nodule, one lesion in segment 7 and possibly at the resection margin. A PET scan was therefore performed 23/08/2010, this showed two FDG positive nodules in the right lung, FDG positive nodes in the right para thraceal aspect and in the sub carinal region, and a single FDG positive lesion in the liver in segment 7. In addition abnormal FDG focus was seen in the presacral aspect which corresponded to presacral excess soft tissue at the level of the anastomosis and the appearances were suspicious for local recurrence.
This patient had two hepatic lesions identified on the pre TACE scan (screening and baseline scan not available), one lesion in segment 2 with longest diameter of 28mm and one lesion in segment 3 with longest diameter 36mm (sum longest diameter 64mm), both assessed as having 10% necrosis. On the pre resection scan the diameters were 36mm and 24mm (sum longest diameter 60mm), both lesions now assessed as having 90% necrosis (i.e. RECIST stable disease, necrosis partial response).
The histology report describes non atomic (wedge) resection sited in segments 2 and 3, and gives the number of lesions as 1: a single lesion with longest tumour diameter 35mm, distance from hepatic resection margin of nearest tumour 30mm, no invasion of adherent adjacent tissue or satellite lesions present. The liver capsule was not intact and smooth, and the macroscopic appearance of the liver was “steatosis”. The necrosis and fibrosis by histology results were: residual tumour 1%, necrosis 89%, fibrosis 10%. The histology report had the comments: “Necrosis with peripheral fibrosis (capsule) only small residual tumour 2-3 glands” and “Some fibrous septa within the necrotic area”. 35

36. Paragon II R0 Resection Patients: R0 16/25 (64%),
Primary Endpoint: tumour resectability of targeted tumours (% of patients with R0 resection, i.e. >2mm clearance margin)
Patients: R0 16/25 (64%),
R1 (<2mm) 9/25 (36%)
Distance from hepatic resection margin of nearest tumour
Data in for n = 25 patients, requested additional data from Vienna.
16/25 (64.0%) patients had distance >2mm for ALL their tumours
9/25 (36.0%) patients had distance <2mm for one or more of their tumours
The Primary Endpoint is Tumour resectability at surgery, further specified by the protocol:
6.2 Primary Endpoint
Tumour resectability of targeted tumours at surgery will be assessed. This will be measured as percentage of patients with R0 resection, where R0 is defined as >2mm clearance margin.
The protocol inclusion criterion 1 says:
1. Presence of potentially resectable colorectal cancer liver metastases, with less than 60% liver tumour replacement. The consulting surgeon, according to local practice, will determine resectability. Refer to Appendix 3 for guidelines on resectability.
Appendix 3 says: 1. Resectable liver metastases are defined as metastases which can be totally resected by surgery.
1. Resectable liver metastases are defined as metastases which can be totally resected by surgery.
- with one or several anatomical resections provided the amount of remnant liver parenchyma after surgery is not less than 30% of total functional parenchyma.
- with one or several wedge resections alone or in combination with anatomical resections.
- the clearance between the tumour margin and the cut surface of the liver should be one centimetre or more whenever possible. However resection with a shorter clearance is acceptable provided all tumour has been removed.
- the number of independent liver metastases observed on preoperative imaging should not exceed four.
- Patients with metachronous metastases must have undergone complete resection of the primary tumour without gross or microscopic evidence of residual disease (R0).
The advice of the Chief Investigator Mr Graeme Poston is that we “Don't need to worry about R0 in this context as we are only meant to be recruiting easily resectable cases.
The end point is simply the feasibility of resection 4 weeks after DC bead TACE.”
Due to a heavy general work load at the histopathology lab at Aintree and Vienna, and that patients have been treated more recently than 2 months ago (expected lead time to get histopathology report), the measure of the minimum distance from the tumour to the resection margin has been completed for 25 of the 39 patients (remaining patients will be assessed as soon as possible). By the definition of the protocol (R0 = >2mm from the tumour to the resection margin) a patient has to have a distance from the tumour to the resection margin of >2mm for all the patient’s tumours in order to be considered R0. This is the case for 16/25 patients (64.0%).
R0 resection should only be summarised on a per patient basis (not also on a per tumour basis, as previously done).
Due to a heavy general work load at the histopathology lab at Aintree, the measure of the minimum distance from the tumour to the resection margin has been completed for 32 targeted tumours (remaining tumours will be assessed as soon as possible). By the definition of the protocol R0 = >2mm from the tumour to the resection margin. This is the case for 26/32 tumours (81%). 36

37. Serious Adverse Events
Two patient deaths
Acute pneumomediastinum, during surgery
Aspiration pneumonitis, post surgery in-patient stay
Eleven Serious Adverse Events
Post embolisation syndrome in 4 patients (15%, expected)
Pancreatitis (expected, TACE related, non-target embol.)
Biloma (expected, surgical complication, MHRA: TACE)
Urinoma (expected, surgical complication, not TACE related)
Paroxysmal atrial fibrillation (not TACE related)
Jaundice (due to recurrence, not TACE related)
Neck haematoma (anaesthetic line complication)
Aspiration pneumonitis (not TACE related)
No serious and unexpected events
Regarding the biloma, which both the Surgeons at Aintree and our medical experts consider a complication of surgery, the MHRA has informed us specifically that they see this as a result of the treatment with the device:
“CI/2008/0016, Serious Adverse Event ref: 2011/002/018/601/003, Biocompatibles ref: SAECA
Dear Karen
Thank you for submitting the report for this serious adverse event in which a patient suffered from a biloma. This report has been reviewed by our clinical team who agreed that the incident seen was an expected side effect of this treatment. However, they were also of the opinion that the incident is a result of the treatment with the device and therefore did not agree with Biocompatibles' conclusion that the incident was unrelated to the device. They are happy for me to close this incident but wanted me to convey this message to you nonetheless.
Kind regards
Clare Huntington
Medical Device Specialist
MHRA”
The pancreatitis occurred in patient Patient J-S (74yo man, adenocarcinoma of the rectum resected in 2009, metastatic disease diagnosed by imaging 19/08/2010), he had TACE in the neoadjuvant study 19/11/2010, during the routine hospital stay following TACE the patient became pyrexial with raised CRP and right upper quadrant pain, date of onset was the day after TACE. Pre-procedure CT and angiography showed an artery passing from the hilum of the liver back towards the pancreas. Although the catheter was positioned distally to this during bead administration (which was lobar, RHL, 160mg, tumour in segment 5, longest diameter 22mm, necrosis by imaging not available, viable tumour by histology 20%) a reflux of beads can not be ruled out. Although non target embolisation of the pancreas is suspected to be the cause of this SAE, rare cases of pancreatitis have been associated with irinotecan therapy, so it is also possible that the event was caused by the chemotherapy. Acute pancreatitis is an unusual but expected adverse event associated with chemoembolisation. This is therefore not considered an unexpected event. In the final analysis the event of acute pancreatitis is considered to be definitely related to the study treatment. 37

38. Outcomes
Histological tumour response (n=26)
16%
23%
61%

39. Surgical findings Often marked capsular ischaemia
Increased inflammatory reaction around tumour
Areas of ischaemia difficult to differentiate from tumour
Ischaemic cholecystitis

40. Patient 1
62 year old male
Previous Segment VIII resection in 2005, with recurrence at site

41. Patient 1 - TACE Treated with 70mg Irinotecan
Discharged at 48 hrs post procedure

42. Patient 1 - 4 weeks post TACE
Right anterior sectionectomy
R0 resection
Complete tumour necrosis
Background steatosis, portal chronic inflammatory change

43. Pre-treatment 1 month post Positive segment 8 Negative segment 4A
Patient 6
Known lesion segment 8
Pre-treatment month post
PET-CT pre-treatment
Positive segment 8 Negative segment 4A

44. Patient 6 histopathology
Treated metastasis
Untreated metastasis

45. Conclusion
Neoadjuvant TACE with Paragon beads is feasible and safe, with acceptable adverse events
R0 resection and tumour necrosis rates are encouraging
No negative effects seen at surgery

46. Conclusion
Future work – explore differential tumour response
Future trials combining DC bead therapy with systemic chemotherapy are now awaited

47. Future trials? Resctable disease
Randomized phase III study with neoadjuvant irinotecan DC bead TACE and perioperative systemic chemotherapy (primary endpoint being PFS)
Unresectable patients
Randomized phase II study looking at benefit of addition of irinotecan DC bead TACE to systemic FOLFOX (primary endpoint being liver resection rate) 47

48. Thank you