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Uveal Melanoma Liver Metastases - 2019 CURE OM Symposium

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Dr. David Eschelman discusses uveal melanoma liver metastases.

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Uveal Melanoma Liver Metastases - 2019 CURE OM Symposium

  1. 1. 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. So what is an interventional radiologist?
  4. 4. 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
  5. 5. 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)
  6. 6. TEAM EFFORT!!!!
  7. 7. Uveal Melanoma Background • Approximately half of patients will develop metastases • 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)
  8. 8. 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
  9. 9. 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? gp100???)
  10. 10. 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.
  11. 11. Uveal Melanoma Background Multiple liver metastases in patient undergoing planned resection of solitary metastasis.
  12. 12. Uveal Melanoma Background Genetic Risk Factors for Metastasis • Monosomy 3 70% of patients die of mets within 4 yrs. Inactivation of BAP1 gene (tumor suppressor) • Partial duplication of 8q (worse) • Gain of 6p (better) • Loss of 1p and 8p Chromosomal heterogeneity!
  13. 13. Metastatic-free Interval According to Genomic Results Br J Ophthalmol 2013-303867
  14. 14. Uveal Melanoma Background Gene Expression Profiling • Class 1 - very low risk of metastasis • Class 2 - very high risk of metastasis (172 patients) J Mol Diagn 2010; 12:461-468
  15. 15. Uveal Melanoma Background Pigment Cell and Melanoma Research 2012; 25:171-181
  16. 16. Surveillance Imaging • Surveillance Scheduling – No consensus: Varies from center to center – Depends on tumor histology and genetics • Dr Sato protocol – Low/intermediate risk: MRI q6-12 mo, CXR q12 mo for 5 years – High risk: MRI q3 mo + CT chest q 6 mo for 2 years, then MRI q6 mo + CT q 12 mo for 3 years
  17. 17. NCCN Guidelines v1.2018 RISK OF DISTANT METASTASIS - Low risk: • Class 1A(x) • Disomy 3 • Gain of chromosome 6p • EIF1AX mutation • T1 (AJCC) (See ST-1 and ST-2) • Spindle cells SYSTEMIC IMAGING BASED ON RISK STRATIFICATION • Imaging to evaluate signs or symptoms as clinically indicated • Consider surveillance imaging(y)
  18. 18. NCCN Guidelines v1.2018 RISK OF DISTANT METASTASIS - Medium risk: • Class 1B(x) • SF3B1 mutation • T2 and T3 (AJCC) (See ST-1 and ST-2) • Mixed histology (spindle and epithelioid cells) SYSTEMIC IMAGING BASED ON RISK STRATIFICATION • Imaging to evaluate signs or symptoms as clinically indicated • Consider surveillance imaging(y) every 6–12 months for 10 years, then as clinically indicated
  19. 19. NCCN Guidelines v1.2018 RISK OF DISTANT METASTASIS - High risk: • Class 2(x) • PRAME mutation • Monosomy 3 • Epithelioid cells • Gain of chromosome 8q • Extraocular extension • BAP1 mutation • Ciliary body involvement • T4 (AJCC) (See ST-1 and ST-2) SYSTEMIC IMAGING BASED ON RISK STRATIFICATION • Imaging to evaluate signs or symptoms as clinically indicated • Consider surveillance imaging(y) every 3-6 months for 5 years, then every 6-12 months for 10 years, then as clinically indicated
  20. 20. NCCN Guidelines v1.2018 Surveillance: The most frequent sites of metastasis are liver, lungs, skin/soft tissue, and bones. At minimum, all patients should have contrast-enhanced MR or ultrasound of the liver, with modality preference determined by expertise at the treating institution. Additional imaging modalities may include chest/abdominal/pelvic CT with contrast. However, screening should limit radiation exposure whenever possible. Scans should be performed with IV contrast unless contraindicated. . . . . . but also add: (y) Recognizing that there are limited options for systemic recurrence and that regular imaging may cause patient anxiety, some patients may elect to forgo surveillance imaging.
  21. 21. 8/11/2010
  22. 22. 10/27/2010
  23. 23. 12/23/2010
  24. 24. 4/09/2010
  25. 25. MRI is better than CT (another example) CT MRI
  26. 26. MRI is better than CT (yet another example) CT MRI
  27. 27. So Does Screening Offer Any Benefit? (Are there treatments that can prolong survival?) Immunocore gp100 (pay attention later today) But let’s move on to evidence supporting liver-directed treatments . . .
  28. 28. So Does Screening Offer Any Benefit? (Are there treatments that can prolong survival?) Mayo Clinic - • 101 patients, Jan 2000 – Aug 2013 • 59% male, median age 62, 92% ECOG 0-1 • Treatment with liver-directed therapy (LDT) was better than systemic treatments LDT 26 months median survival Bevacizumab 12 Ipilimumab 13 Kinase inhibitors 13 (though patients undergoing LDT were in somewhat better condition prior to starting treatment) Melanoma Research 2015; 25:59-63
  29. 29. So Does Screening Offer Any Benefit? (Are there treatments that can prolong survival?) Jefferson Experience - • Compared 101 patients presenting with liver metastases 1971 – 1993 (81% treated with DTIC-based systemic treatments) to 655 patients 2000 – 2017 (88% started treatment with liver-directed therapy) • Primary eye tumors were similar in size, thickness, and distribution of location between both cohorts • In those patients who developed liver metastases, the median time from eye tumor treatment to death was 3.4 years in the early cohort vs. 5.0 years in the later cohort. Journal of Clinical Oncology 2018; 36: 9592s
  30. 30. Initial Presentation MRI was normal 6 months ago
  31. 31. Rapid Growth without Treatment 12/17/2013 4/30/2014 6/2/2014

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