Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Liver Directed Therapies

314 views

Published on

Presentation by David J. Eschelman, MD, FSIR. Presented at the 2018 Eyes on a Cure: Patient & Caregiver Symposium, hosted by the Melanoma Research Foundation's CURE OM initiative. 

Published in: Health & Medicine
  • Secrets To Working Online, Hundreds of online opportunites you can profit with today! ●●● http://ishbv.com/ezpayjobs/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • How I Cured My Yeast Infection, Ex Sufferer reveals secret system, For Lasting Candida Freedom ♣♣♣ https://tinyurl.com/y3flbeje
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • I was searching for a way to explain my recently frequent yeast infections and other related conditions stumbled upon your program on the internet. I suffered from chronic mouth thrush (with creamy white lesions on my tongue and inner cheeks). My baby daughter had the same problem in her mouth and your program was the only thing that helped us! I highly recommend your book to anyone who is perceptive about their health, and for those who are tired of being told that it's all in their heads. I feel so rejuvenated and lucky to have found this system. ★★★ http://ishbv.com/index7/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • I went from getting $3 surveys to $500 surveys every day!! learn more...  https://tinyurl.com/make2793amonth
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Earn $500 for taking a 1 hour paid survey! read more... ▲▲▲ https://tinyurl.com/realmoneystreams2019
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

Liver Directed Therapies

  1. 1. 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
  2. 2. Disclosures • I will discuss unapproved uses of commercial products. • I am a not a consultant for anyone!
  3. 3. 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
  4. 4. 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)
  5. 5. TEAM EFFORT!!!!
  6. 6. 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)
  7. 7. 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
  8. 8. 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???)
  9. 9. 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.
  10. 10. Uveal Melanoma Background Multiple liver metastases in patient undergoing planned resection of solitary metastasis.
  11. 11. MUM Treatments (Metastatic Uveal Melanoma) Liver-Directed Therapies • Immunoembolization • Radioactive microspheres • Chemoembolization, Drug-eluting beads • Fotemustine infusion • IHP/PHP • Ablation
  12. 12. 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
  13. 13. Immunoembolization at Jefferson Takami Sato, M.D., Ph.D. Kevin L. Sullivan, M.D. Michael J. Mastrangelo, M.D.
  14. 14. 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.
  15. 15. 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
  16. 16. 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
  17. 17. 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
  18. 18. 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
  19. 19. Immunoembolization Initial 2 months later
  20. 20. Immunoembolization Initial 2 months later
  21. 21. 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
  22. 22. 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
  23. 23. 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
  24. 24. 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)
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. Immunoembolization of the Hepatic Artery with Granulocyte-Macrophage Colony Stimulating Factor Phase II Trial JVIR 2015; 26:523-532
  29. 29. 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
  30. 30. 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!
  31. 31. 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
  32. 32. Immunoembolization - Lipiodol Distribution MRI pre-treatment CT scan post-treatment
  33. 33. Prolonged Survival Following Immunoembolization 10/2010 3/2018
  34. 34. 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!)
  35. 35. Progression Despite Immunoembolization Initial 2 months later
  36. 36. Additional MUM Treatments (Metastatic Uveal Melanoma) • Radioactive microspheres • Chemoembolization (Drug-eluting beads) • Percutaneous hepatic perfusion (PHP) • Ablation
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. SIRspheres Prior to Treatment 11 months after Treatment
  43. 43. Rapid Tumor Progression Prior to SIRspheres 2 months after SIRspheres
  44. 44. 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
  45. 45. 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
  46. 46. 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
  47. 47. 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
  48. 48. BCNU Chemoembolization First Treatment 13 months later
  49. 49. BCNU Chemoembolization First Treatment Second Treatment
  50. 50. DEBDOX
  51. 51. 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
  52. 52. 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
  53. 53. 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
  54. 54. 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)
  55. 55. 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
  56. 56. DEBDOX/BCNU for MUM Size of Largest Tumor JVIR 2014; 25: S45
  57. 57. DEBDOX/BCNU for MUM Results JVIR 2014; 25: S45 Nodular vs Infiltrative Disease Nodular Infiltrative Time (months) SurvivalProbability(%)
  58. 58. 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
  59. 59. • 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
  60. 60. 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!)
  61. 61. DEBDOX Initial 10 months later
  62. 62. DEBDOX Pre-Treatment 2 months later
  63. 63. DEBDOX Pre-Treatment 12 months later
  64. 64. Drug-eluting Beads + Adriamycin, Followed by Chemoembolization Initial 4 months later
  65. 65. Drug-eluting Beads + Adriamycin, Followed by Chemoembolization Initial 15 months later
  66. 66. 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
  67. 67. Percutaneous Hepatic Perfusion
  68. 68. 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
  69. 69. 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
  70. 70. 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. 71. 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. 72. 72 DELCATH SYSTEMS, INC Phase III OcMel Trial Participating Centers (US)
  73. 73. Percutaneous Hepatic Perfusion AnesthesiaVenovenous Bypass Perfusionist 2 IR Attendings IR Nurses and Technologists Research Coordinators
  74. 74. 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
  75. 75. 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.
  76. 76. 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!!!
  77. 77. 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)
  78. 78. From a grateful patient who also donated/raised > $600,000 for the MUM program.

×