Treatment of Uveal Melanoma
Metastatic to the Liver
David J. Eschelman, M.D., FSIR
Professor of Radiology,
Sidney Kimmel Medical College of Thomas Jefferson University
Co-Director of Interventional Radiology,
Thomas Jefferson University Hospital

Disclosures
• I will discuss unapproved uses of
commercial products.
• I am a not a consultant for anyone!

MUM at Jefferson
(Metastatic Uveal Melanoma)
• National referral center
• 2/3 of our patients live outside of PA, NJ, DE
• Weekly MUM multidisciplinary conference
(Medical Oncologist, IR, MRI, +/- Rad Onc)
• Weekly MUM multidisciplinary clinic
• > 650 hepatic embolization procedures/yr.
• Approx. 1/4 – 1/3 of primary UM tumors in
U.S. initially treated at Wills Eye Hospital
An “Orphan Disease” that has Found a Home at Jefferson

Dr. Marlana Orloff (Medical
Oncology)
Drs. Eschelman (IR), Sato (Medical
Oncology) and Gonsalves (IR)
Dr. Robert Adamo (IR)
MUM PHYSICIANS
Dr. Rani Anne
(Radiation
Oncology)

TEAM EFFORT!!!!

Uveal Melanoma
Background
• Liver is predominant organ of involvement in >90% of
patients with metastases, and tends to be first (and
in half only) manifestation of the disease
• Other sites of metastases include lungs, bone, brain,
subcutaneous tissues, other visceral organs/peritoneum
• Clinical course of patients with metastases is generally
determined by progression of the disease in the liver
• Pattern of metastases very different from cutaneous
melanoma (lymph nodes, lung, subcutaneous tissues)

Uveal Melanoma
Background
• Improved treatment of the primary tumor
has not resulted in prolonged survival
• Hematogenous micrometastases have
occurred prior to diagnosis of eye tumor

Uveal Melanoma
Background
• Unlike cutaneous melanoma, there is no effective
systemic chemotherapy regimen for MUM.
• Unlike cutaneous melanoma, immune checkpoint
blockade therapy has a poor response (<<5%) and
high complication rate. No BRAF mutation with
MUM.
• There is no proven adjuvant therapy for patients at
high risk for developing metastases. (Sutent?
Valproic acid? GP100???)

Uveal Melanoma
Background
• Because the clinical course of most patients
with MUM is based on the status of the
disease in the liver, loco-regional therapy is
important for control of the metastases since
there is no effective systemic therapy.
• Surgery and ablation techniques are rarely
useful due to multiplicity of tumors. Very
high recurrence rate following surgical
resection within 5 yr. of initial UM diagnosis.

Uveal Melanoma
Background
Multiple liver
metastases in
patient
undergoing
planned resection
of solitary
metastasis.

MUM Treatments
(Metastatic Uveal Melanoma)
Liver-Directed Therapies
• Immunoembolization
• Radioactive microspheres
• Chemoembolization,
Drug-eluting beads
• Fotemustine infusion
• IHP/PHP
• Ablation

Chemoembolization
Carin F. Gonsalves, M.D.
Author Pt # Drug (s) OS Resp* OS Non-Resp Median OS
Mavligit ’88 30 Cisplatin 14 6 11
Cantore ’94 8 Carboplatin -- -- 15
Bedikian ’95 44 Cisplatin 14.5 5 6
Sato ’95 14 Cisplatin -- -- 6.6
Patel ’05 24 BCNU (100mg) 21.9 3.3 5.2
Huppert ’09 14 Cisplatin/Carboplatin 14.5 10 11.5
Vogl ’07 12 Mitomycin C 21 16.5 21
Dayani ’09 21 Mitomycin C, Cisplatin,
Doxorubicin
12.7 3.7 7.6 (mean)
Gupta ’10 125 Mostly Cisplatin 15.8 6.1 6.7

Immunoembolization at Jefferson
Takami Sato, M.D., Ph.D.
Kevin L. Sullivan, M.D.
Michael J. Mastrangelo, M.D.

Immunoembolization
Rationale
• Destruction of tumor by embolization would control
tumor progression locally and provide tumor antigens to
the local immune system
• Concurrent use of biological response modifier(s) induces
an inflammatory response in the tumor and surrounding
tissue which may improve the antigen presentation to the
local immune system
• Local stimulation of the immune system may result in the
development of a systemic immune response against
tumor cells which may suppress the growth of untreated
tumors
• IE could potentially create an in situ tumor vaccine.

Immunoembolization
Granulocyte-Macrophage Colony-Stimulating Factor
• Glycoprotein secreted by activated T cells
• LEUKINE (sargramostim) is a recombinant yeast-
derived human GM-CSF
• Increases myeloid cell production
• Stimulates macrophages
• Increases cytotoxicity of monocytes toward tumor
cell lines
• Promotes maturation of dendritic cells

Immunoembolization
Selection of GM-CSF
Vaccination was performed with 10 tumor cell
lines engineered to secrete different cytokines
Proc Natl Acad Sci 1993; 90: 3539-3543

Immunoembolization
Phase 1 Study – Intro
• Purpose was to investigate feasibility and safety
• 2000 – 2004, single institution
• 34 of 39 patients had MUM
• <50% tumor involvement, unresectable
• Lobar hepatic artery embolization every 4 weeks using
escalating dose of GM-CSF (25-2000 mcg) emulsified
with Ethiodol followed by Gelfoam, for 6 treatments
• Imaging (CT, MRI) and clinical assessment after
every other treatment to assess response (RECIST)
• Primary end-points were dose-limiting toxicity and
maximum tolerated dose
J Clin Oncol 2008; 26:5436-5442

Immunoembolization
Phase 1 Study – Results (n=34)
• 6 procedures/patient (median, range 1-14)
• 32% responded (2 CR, 8 PR)
• 32% stable disease
• OS: 14.4 months (median)
(33.7 months for CR/PR, 12.4 months SD/PD)
• Survival: 1 yr. 62%, 2 yr. 26%
• PFS-liver: 4.8 months (median)
• PFS-systemic: 10.4 months (median)
J Clin Oncol 2008; 26:5436-5442

Immunoembolization
Initial 2 months later

Immunoembolization
Initial 2 months later

Immunoembolization
Dose-Related Response (n=31)
Patients undergoing high-dose IE (>1500 mcg) vs.
low-dose IE (<1000 mcg):
• Longer OS (20.4 vs. 13.0 months, median)
• Longer PFS-L (9.3 vs. 4.2 months, median)
• Longer PFS-S (12.4 vs. 5.6 months, median)*
* P < .05
Radiology 2009; 252:290-298

Immunoembolization
Comparison to BCNU TACE
Patients undergoing high-dose IE (>1500 mcg) vs.
TACE with BCNU (TJUH Phase II study, excluding
patients with >50% tumor burden in liver):
• Longer OS (20.4 vs. 9.8 months, median)*
• Longer PFS-L (9.3 vs. 6.4 months, median)
• Longer PFS-S (12.4 vs. 4.8 months, median)*
* P < .05
Radiology 2009; 252:290-298

Immunoembolization
Comparison to BCNU TACE
• No significant difference in overall or progression-free
survival between patients who received BCNU TACE
and lower dose IE
• Stabilization of hepatic metastases was most likely
achieved by the ischemic effects of embolization rather
than by the administered medication
• Systemic progression was delayed in the high-dose IE
group, suggesting an induction of a systemic immune
response against the melanoma cells

Immunoembolization
Additional observations -
• Tumor regression was sustained after discontinuation of
immunoembolization in several patients
• Response can take as long as 4 months (4 IE procedures)
• Evidence of activation of the memory cell arm of the
immune system (T cells), suggesting a tumor vaccine
Repeated immune stimulation has been shown to be
necessary to overcome tolerance and induce a vigorous
response (J Exp Med 1997; 186: 645-653 & J Clin Invest 1998; 101:2406-2414)

Immunoembolization of the Hepatic Artery with
Granulocyte-Macrophage Colony Stimulating Factor
• R21 study
• Randomized, double blind, phase II clinical study for
MUM patients
• Primary endpoint – regression of liver mets
• Secondary endpoint – time to progression, overall survival,
and development of local/systemic immune response
• 52 patients – randomized to receive embolization using
Ethiodol, with or without 2000 mcg GM-CSF, followed by
Gelfoam
• Stratified by liver involvement (<20% vs. 20-50%) and
HLA-A2 status

Immunoembolization of the Hepatic Artery with
Granulocyte-Macrophage Colony Stimulating Factor
• Excludes patients with >50% tumor involvement,
extrahepatic mets, prior local liver therapies
• Lobar treatments every 4 weeks with imaging (CT, MRI)
and clinical assessment every 8 weeks (RECIST)
• Investigation of biopsy specimens before/after treatment
• Analysis of peripheral blood mononuclear cells and serum
to assess systemic immune response
• 52 patients enrolled beginning June 2005
• Last treatment under protocol April 2010
• 2 completed (24 months)
• 51 patients (98%) are deceased

Immunoembolization of the Hepatic Artery with
Granulocyte-Macrophage Colony Stimulating Factor
Results – Phase II Trial
• Both immunoembolization (IE) and bland embolization were
well tolerated with acceptable toxicity
• Both approaches induced cytokine productions, more
prominent in patients treated with IE
• IE showed a potential overall survival benefit in patients with
20-50% tumor replacement
• Trend towards longer PFS-S following IE
• Unexpectedly, PFS-L was shorter following IE in patients
with <20% tumor involvement, suggesting a suppressive
(paradoxical) response to high dose GM-CSF
JVIR 2015; 26:523-532

Immunoembolization of the Hepatic Artery with
Granulocyte-Macrophage Colony Stimulating Factor
Phase II Trial
JVIR 2015; 26:523-532

Immunoembolization
Phase II Trial - Results
• Not powered to determine survival benefit; designed as proof
of concept study to investigate hypothesis that adding GM-CSF
to embolization would increase release of pro-inflammatory
cytokines and delay development of extrahepatic metastases
• Plain embo – increases in IL-6 and IL-8 > 18 hrs.
• Immunoembo – significant (P<0.001) and rapid increase in
TNF-a, IL-6, and IL-8 at 1 and 18 hrs post treatment,
suggesting faster and more robust inflammatory response
• Increased IL-6 level at 1 hr and IL-8 level at 18 hrs correlated
with delay in onset of extrahepatic metastases with a dose-
response pattern
• Double-blind, randomized clinical trial comparing bland
embolization to drug + embolization, showing a benefit of
adding the drug

Immunoembolization
1500 mcg GM-CSF
JVIR 2014; 25: S26
• 68 patients treated 3/2004 – 6/2013, retrospective
• 37 (54%) had < 20% tumor burden
31 (46%) had 20-50% tumor burden
• 42 patients (62%) with stable disease
• 12 patients (18%) with radiologic response: CR=3, PR=9
• Median OS 18.9 months (range 2.1 – 52.2)
28 patients (41%) remain alive at time of analysis
It took us 14 years to figure out (what we
think is) the appropriate dose of GM-CSF!

Immunoembolization
1500 mcg GM-CSF
JVIR 2014; 25: S26
Median Survival in
Months
<20% Liver
Involvement
20-50% Liver
Involvement
OS 24.0 16.8
PFS - Liver 5.9 4.4
PFS – Systemic
p = 0.004
9.2 5.5

Immunoembolization - Lipiodol Distribution
MRI pre-treatment CT scan post-treatment

Prolonged Survival Following Immunoembolization
10/2010
3/2018

Prolonged Survival Following Immunoembolization
Work in Progress . . . . .
• 174 patients treated 6/2005 – 12/2014, retrospective
• Median OS: 17 months (range 2 – 83++)
• 28 (16%) patients have prolonged survival (> 3 yr.)
and treatment breaks
Of these 28 “Superstars” . . . . .
• At least 50% lived > 4 years (will increase!)
• At least 18% lived > 6 years (will increase!)

Progression Despite Immunoembolization
Initial 2 months later

Additional MUM Treatments
(Metastatic Uveal Melanoma)
• Radioactive microspheres
• Chemoembolization
(Drug-eluting beads)
• Percutaneous hepatic perfusion (PHP)
• Ablation

Transarterial Catheter-Directed
Treatment of Liver Tumors
• Radioembolization (RE)
• 20-60 micron-sized particles loaded with a radioactive isotope
(Yttrium-90) are injected into the hepatic artery
• Radioactive particles lodge within arteries supplying tumors,
emit radiation and destroy cancer cells
Radioactive Microspheres

Y-90 Embolization for MUM
Jefferson Experience, Salvage Therapy
• 32 MUM patients
• Single institution, retrospective
• Jan 2007 – Apr 2009; follow-up to Sept 2009
• 14 M, 18 F; median age 61
• All patients had progressed followed IE or TACE
(median 9, 1-23 prior embolization procedures)
• Pre-treatment tumor burden:
< 25% (n=25)
25-50% (n=5)
>50% (n=2)
AJR 2011; 196:468-473

Y-90 Embolization for MUM
Jefferson Experience, Salvage Therapy
Results
• OS 1 – 29 months (median 10)
• Median survival longer for patients with pretreatment tumor
burden of < 25% vs. >25% (10.5 vs. 3.9 months)*
• Best radiologic response (RECIST):
CR 1
PR 1
SD 18
PD 12
• Median survival longer for patients with CR, PR, or SD vs.
PD (14.7 vs. 4.9 months)*
*P < .05
AJR 2011; 196:468-473

Y-90 Embolization for MUM
Jefferson Experience, Updated
• 71 patients, 82% salvage
• Median PFS-L 5.9 months
• Median OS after treatment 12.3 months
• Median OS following diagnosis of liver mets
23.9 months (range, 6.2 – 69 months)
• Low pre-treatment TGA (total glycolic
activity) was associated with a significantly
longer median OS (17.2 vs. 9.7 months,
p=0.01)
American Journal of Clinical Oncology 2016; 39:189-195

Y-90 Embolization for MUM
Phase II, Single Institution, Prospective Trial
• 48 patients, November 2011 – January 2017
• 24 treatment naïve, 24 progressed after
immunoembolization
• All abstracts are confidential from the time of submission until the time of
public release by ASCO. The majority of abstracts, including your abstract,
will be released by ASCO on May 16, 2018, at 5:00 PM EDT on
meetinglibrary.asco.org. As the lead author of this abstract, you agreed to
abide by ASCO’s Confidentiality Policy on behalf of all parties involved
with the abstract when you originally submitted the abstract.
Journal of Clinical Oncology – ASCO 2018

SIRspheres
Prior to Treatment 11 months after Treatment

Rapid Tumor Progression
Prior to SIRspheres 2 months after SIRspheres

Chemoembolization
Carin F. Gonsalves, M.D.
Author Pt # Drug (s) OS Resp* OS Non-Resp Median OS
Mavligit ’88 30 Cisplatin 14 6 11
Cantore ’94 8 Carboplatin -- -- 15
Bedikian ’95 44 Cisplatin 14.5 5 6
Sato ’95 14 Cisplatin -- -- 6.6
Patel ’05 24 BCNU (100mg) 21.9 3.3 5.2
Huppert ’09 14 Cisplatin/Carboplatin 14.5 10 11.5
Vogl ’07 12 Mitomycin C 21 16.5 21
Dayani ’09 21 Mitomycin C, Cisplatin,
Doxorubicin
12.7 3.7 7.6 (mean)
Gupta ’10 125 Mostly Cisplatin 15.8 6.1 6.7

Chemoembolization
MD Anderson
Am J Clin Oncol 2010; 33:474-480
• 125 patients (Jan 1992 – Dec 2005)
• 122 patients received cisplatin; 65 also received
arterial infusion of vinblastine (n=54) or
vinblastine/dacarbazine (n=11) afterwards
• Tumor burden:
< 25% 36 patients (32%)
25-50% 41 (36%)
>50-75% 25 (22%)
>75% 11 (10%)
• Relatively high rate of complications (14%),
many severe

Chemoembolization
MD Anderson
Am J Clin Oncol 2010; 33:474-480
• Overall Survival 6.7 months (median, n=113):
< 25% 14 months
25-50% 5.1
>50-75% 5.5
>75% 2.4
• Overall Survival based on LDH:
Normal 20 months
>1 but <2 x normal 11
> 2 x normal 3.6
• Recommend against treatment when >75%
tumor replacement

Chemoembolization
BCNU
• 50 patients with >50% tumor replacement
at presentation (Jan 2004 – Nov 2011)
• 200 mg BCNU
• Median survival 7.1 months
• 22% 1 yr. survival (12.2 – 32.3 months)
• 72% had stable disease or a treatment response
• Neither pre-treatment LDH (> or < 500) nor
tumor burden (50-59%, 60-75%, > 75%) had
effect on survival
AJR 2015; 205:429-433

BCNU Chemoembolization
First Treatment 13 months later

BCNU Chemoembolization
First Treatment Second Treatment

DEBDOX

Drug-Eluting Beads for MUM
Irinotecan
in vivo 2009; 23:131-138
• 10 patients in 2 institutions (Ferrara, Florence)
• Jan 2007 – June 2008
• 8 M, 2 F; mean age 65
• All patients had prior systemic chemo/immunotherapy
• Pre-treatment tumor burden:
< 25% (n=3)
25-50% (n=4)
50-75% (n=3)
• Assessment by 3-phase CT pre/post treatment
• 100-200 mg Irinotecan administered in 2-4 ml of
100-300/300-500 micron DC Beads
• Half had one treatment, other half had 2 treatments

Drug-Eluting Beads for MUM
Irinotecan
in vivo 2009; 23:131-138
• All 10 patients obtained an objective response!
• Tumor reduction by imaging:
90% (n=3)
80% (n=3)
60-70% (n=4)
• Median follow-up 6.5 (range 4 – 9) months
• 8 patients alive at time of report; 2 died at 4 and 6 months
• Response related to degree of initial tumor involvement
• Side effects similar to TACE, no alopecia or bone
marrow toxicity

Drug-Eluting Beads for MUM
Irinotecan
Annals of Gastroenterology and Hepatology 2012; 3:9-14
• Single arm, phase II clinical trial
• Jan 2007 – Feb 2010, 52 patients
• All patients had prior systemic chemo/immunotherapy
• Pre-treatment tumor burden:
< 25% (n=30, 58%)
25-50% (n=20, 38%)
50-75% (n=4, 8%)
• 85 procedures (median 1.6/patient)
• No complications, limited toxicity, + abdominal pain
• 100 mg IRI x 10 patients, remainder 200 mg IRI

Drug-Eluting Beads for MUM
Irinotecan
Annals of Gastroenterology and Hepatology 2012; 3:9-14
• No complications, limited toxicity, + abdominal pain
• Tumor reduction by imaging (“necrosis and reduction of
contrast enhancement”):
> 90% (n=17)
80-90% (n=30)
60-80% (n=3)
• PFS-L 7.5 months, OS 13.9 months (both median)

DEBDOX/BCNU for MUM
JVIR 2014; 25: S45
• 19 patients, no prior treatments
• July 2011 – January 2013, retrospective review
• Poor candidates for other liver-directed therapies
(Tumors > 5 cm, > 50% tumor burden, rapid growth)
• < 4 ml 100-300 micron LC Beads/150 mg adriamycin
(14/36 treatments received full dose)
• 13/19 patients proceeded to BCNU chemoembolization
(73 treatments)
• Based on disparate response, patients divided into
“nodular” vs. “infiltrative” pattern, based on MRI
appearance

DEBDOX/BCNU for MUM
Size of Largest Tumor
JVIR 2014; 25: S45

DEBDOX/BCNU for MUM
Results
JVIR 2014; 25: S45
Nodular vs Infiltrative Disease
Nodular
Infiltrative
Time (months)
SurvivalProbability(%)

Nodular (n=11): 3 PR, 7 SD, 1 PD
Infiltrative (n=8): 1 PR, 3 SD, 4 PD
JVIR 2014; 25: S45
Survival Mean (mos) 95% CI
Median
(mos) 95% CI
Nodular 22.8 15.7 - 29.8 16 ---
Infiltrative 4.7 1.6 - 7.9 2.9 1.8 -7.9
Overall 16.0 11.6 - 20.4 9.1 2.9 -12.8
Chi-square = 8.4
p value = 0.0037
DEBDOX/BCNU for MUM
Results

• 2008 study includes cutaneous and uveal melanoma
• Do not report tumor burden or size
• Nodular/infiltrative pattern is determined by angiography (we use
MRI.) Infiltrative pattern significantly more likely to be ciliary
body tumors with extrascleral extension, and loss of tumor
suppressor gene (LZTS1 on 8p).
Survival (mos)
#
pts
Tx Nodular Infiltrative
Sharma KV, et
al (2008)
20 CAM 20 3.8
Dayani PN, et
al (2009)
21 CAM 12.7 3.7
Chemoembolization: Nodular vs. Infiltrative

DEBDOX/BCNU for MUM
Work in progress . . . .
• added 7 more patients, no prior treatments
• July 2011 – December 2014, retrospective review
• Poor candidates for other liver-directed therapies
(Tumors > 5 cm, > 50% tumor burden, rapid growth)
• OS (patients with NODULAR pattern):
- 18.2 months (median)
- 3/16 (19%) patients still alive
(5 - 7 years after starting treatment!)

DEBDOX
Initial 10 months later

DEBDOX
Pre-Treatment 2 months later

DEBDOX
Pre-Treatment 12 months later

Drug-eluting Beads + Adriamycin, Followed by Chemoembolization
Initial 4 months later

Drug-eluting Beads + Adriamycin, Followed by Chemoembolization
Initial 15 months later

66 DELCATH SYSTEMS, INC
Percutaneous Hepatic Perfusion
• PHP utilizes 3 primary principles:
o ISOLATION – isolates hepatic blood flow
o INFUSION – Melphalan agent delivered to liver via hepatic artery
o FILTRATION – blood from the liver is filtered to reduce Melphalan concentration prior to returning the blood
to systemic circulation
INTERNAL-CONFIDENTIAL

Percutaneous Hepatic Perfusion

Percutaneous Hepatic Perfusion
J Surgical Oncology 2017 (online):
• Moffitt (FL) + Southampton (UK)
• 51 patients, 12/2008 – 10/2016, retrospective
• 15 completed planned course (4 or 6 treatments)
• 7 still undergoing treatment
• 29 patients discontinued early:
- 9 treatment-related toxicity
- 17 disease progression
- 3 patient preference
• Median of 2 treatments in UK, 3 in FL

Percutaneous Hepatic Perfusion
J Surgical Oncology 2017 (online):
• 6% CR + 43% PR
• 33% SD at 3 months, 22% at 6 months
• Median OS 15.3 months; 1 yr survival 65%, 2 yr. 37%
• No treatment-related fatalities, but . .. . . .
- 3 VTach, 1 SVT
- 5 myocardial ischemia (1 MI, 1 pulmonary edema)
- 3 major bleeding (DIC, abdominal, cerebral)
- 2 pulmonary edema, 2 pulmonary emboli
- DVT: LE x 2, IVC, IJ, access site
- Transfusions: 47% PRBCs, 78% platelets
- 4 episodes neutropenic sepsis with 31% experiencing
severe neutropenia

Percutaneous Hepatic Perfusion vs Best Alternative Care in
Patients With Hepatic-dominant Ocular Melanoma (FOCUS)
• Randomized, prospective trial
• PHP vs. BAC
- Chemoembolization, ipi, pembro, dacarbazine
• 240 patients (120 in each arm)
• < 50% of the liver replaced by tumor, very limited
extrahepatic disease
• 35 sites “recruiting:” 13 USA, 22 Europe
• (Jefferson has treated the most patients in this trial!)
• New generation of filters to hopefully reduce bone
marrow toxicity

71 DELCATH SYSTEMS, INC
Global Phase III Clinical Trial
Clinical Trial For Patients with Hepatic-
Dominant Ocular Melanoma
Melphalan/HDS
TX every 6-8 weeks ≤ 6 cycles
BAC
Dacarbazine,TACE, ipilimumab, or
pembrolizumab determined by
institution SOC
Primary Endpoint
(Overall Survival)
Secondary Endpoints
(Progression Free Survival, Objective
Response Rate)
Safety, Pharmacokinetics,
QoL
(Rigorous Analyses to Assess
Risk/Benefit Profile)
Multinational, Multicenter
Randomized Phase 3 Trial in
Patients with Hepatic Dominant
Ocular Melanoma
(N=240)
R 1:1
Phase III Ocular Melanoma Trial

72 DELCATH SYSTEMS, INC
Phase III OcMel Trial Participating Centers (US)

Percutaneous Hepatic Perfusion
AnesthesiaVenovenous
Bypass
Perfusionist
2 IR Attendings
IR Nurses and
Technologists
Research
Coordinators

Microwave Ablation
• Microwave needle is placed
directly into the liver tumor
• Using CT or US guidance
• Generates heat to destroy
tumor cells
• Reserved for patients with a
solitary metastasis or for a
single “rogue” tumor that
won’t respond to
transarterial liver-directed
therapies
Microwave
needle

Microwave Ablation
IE treatments starting 10-16-2012. All tumors
responded except for one.
7/12/17 MRI shows completely necrotic tumor
Microwave ablation 4/20/16
performed by Dr. Adamo
Currently enjoying a long treatment break, 5.5
years after initiating treatment at TJUH.

Current Jefferson Treatment Algorithm
for Liver Metastases in MUM Patients
Following consideration of resection/ablation (rare):
If < 50% liver involvement, limited extrahepatic mets:
• Immunoembolization (especially minimal disease)
• SIRspheres
If < 50% liver involvement, limited extrahepatic mets,
largest tumor > 5-6 cm:
• DEBDOX followed by BCNU Chemoembolization
If > 50% liver involvement with liver dominant disease:
• Chemoembolization (BCNU, DEBDOX)
Progression following immunoembolization:
• SIRspheres (<50% tumor burden)
• Chemoembolization (BCNU, DEBDOX)
Clinical Trials (including Delcath/PHP)! gp100!!!

Future Considerations when Evaluating
Treatment of Liver Metastases in MUM Patients
Comparison of Treatments and Stratification of
Results based on –
• Tumor Burden
• Tumor Genetics
• Pattern of Disease in the Liver
(nodular vs. infiltrative)
Adjust for delay in treatment of one lobe of the
liver when using liver-directed treatments in
clinical trials (allow repeat baseline MRI)

From a grateful patient who also donated/raised > $600,000 for the MUM program.