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ILCA 2019: Tumor Board

ILCA 2019: Tumor Board. Masatoshi Kudo MD, PhD (Japan) Neehar Parikh, MD (USA), and Gonzalo Sapisochin , MD, PhD (Canada) Speaker: Jasmine Sinha , MD (USA) Laura Kulik MD (USA). Disclosures. Laura Kulik (Chair) Eisai: Speaker, Advisory Board Gilead: Speaker Merck: Consulting

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ILCA 2019: Tumor Board

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  1. ILCA 2019: Tumor Board Masatoshi Kudo MD, PhD (Japan)Neehar Parikh, MD (USA), and Gonzalo Sapisochin, MD, PhD (Canada) Speaker: Jasmine Sinha, MD (USA) Laura Kulik MD (USA)

  2. Disclosures Laura Kulik (Chair) • Eisai: Speaker, Advisory Board • Gilead: Speaker • Merck: Consulting • Exelixis: Consulting, Advisory Board • Dova: Speaker • Bayer: Consulting • CE Outcomes: Consulting Jasmine Sinha (Speaker) • None

  3. Case 1 • 53 yo M with pmhx of HCV (G3A)/ETOH cirrhosis c/b HCC with PVT in right PV (V3), AFP 332, plt 58,000, TB 0.9, INR 1.4, albumin 2.8 (MELD 21, CP Class A = 6) • 7/2016: multifocal HCC, 2 lesions (BI-LOBAR), largest 3.2cm • 7/2016: Biopsy consistent with moderately differentiated HCC • 7/28/16: seen by surgery, was deemed not a resection or OLT candidate • Treated with DEB 08/16 • Sir-Sphere 10/19/16: Right Whole • Sir-Sphere 11/7/16: Segment 4A • Started on Sorafenib 12/16 • Referred to second transplant center (NW) for second opinion regarding OLT 12/16: AFP 65, DCP 21

  4. Case 1 OSH PVT demonstrated

  5. Case 1 • At this time what would you advise patient regarding OLT? • “He unfortunately does not appear to be an OLT candidate with multifocal HCC with PVT” • Patient returns to referring institution

  6. Case 1 • Patient returns to NW 08/17; 13 months since diagnosis • Continued on Sorafenib • He developed ascites requiring diuretics after inguinal hernia repair • AFP 14.7, DCP 67, TB 2.7, INR 2.0, Albumin 2.6 (CP Class C = 10)

  7. Case 1 • MRI 08/07/17: 13 mo. Post HCC DX 1.  Cirrhotic liver with 1.7 cm segment 2 lesion demonstrating signal characteristics diagnostic of a hepatocellular carcinoma.2.  Post-treatment changes of the right hepatic lobe without any definite evidence of viable residual tumor.3.  No evidence of portal vein thrombus.4.  Portal hypertension with splenomegaly, gastroesophagealvarices, and moderate volume ascites Chest CT negative with metastatic disease. OLT CANDIDATE?

  8. Transplantation for HCC • OLT represents the highest chance for cure in HCC relative to other options • OLT is reserved for unresectable HCC • HCC is the indication for OLT in 15-50% of centers • Choose wisely…. to avoid misappropriation of limited resource LT benefit = OS w/ LT – OS w/ non-LT options SapisochinG.Nat Rev GastroenterolHepatol. 2017 Apr;14(4):203-217

  9. PVT Treated With SIRT Prior to LT • Single center; Italy 143 transplanted for HCC • 22 treated with Y90 (Sir-Sphere); 4 PVT with CR Patient Characteristics RFS 39 mo. Radiographic & Pathologic Findings Levi Sandri B et al. HepatoBiliary Surg Nutr2017;6(1):44-48.

  10. Wei X, et al. J Clin Oncol 2019

  11. Results • Patient selection • Inclusion of main PVT (SARAH) • Bilirubin levels up to 2.9 mg/dl (SARAH) • SIRT (resin) administration • 20% lung shunt used as cut off • Performed in geographic locations that SIRT ? availability limited outside a trial setting • No boosted Y90 dose • Allowance for only 1 SIRT(SIRveNIB) • 3 week delay of SIRT (not taken into account in ITT) Selection Criteria Median OS Boosted Y90 > 205 Gy: 21 mo. “Good” candidates: 17.5 mo. Score 0: 32. 2 mo.

  12. Prognostic Score in HCC with PVT Treated SIRT (Glass) • 120 patients with HCC with PVT (excluded main PVT) Meta-analysis of CP A-/B7 with + PVT: -1 yr. OS: 37% (95% CI 26-50%) - 3 yr. OS: 13% (95% CI 9-18%) Spreafico C et al. J of Hepatol 2018;68:724-732. Rognoni C et al Oncotarget 2016;7:72343-55. .

  13. Case 1 • Patient was considered for liver transplant with LDLT • Do tumor markers impact this decision? • AFP 14.7, DCP 67 • Does the presence of presumed new lesion in segment 2 impact decision regarding LDLT? • Would you perform LRT to 1.7 cm untreated lesion in segment 2? • Any special considerations from a surgical standpoint due to history of V3 PVT?

  14. HCC recurrence • Retrospective study 313 HCC pts. s/p LT • N = 127 with pre-LT biomarkers • N = 41 HCC recurrence post OLT • 80th percentile cutoff: • AFP ≥ 250 ng/ml, DCP ≥ 7.5 ng/ml, AFP L3 ≥ 35%, Absolute AFP L3≥ 56 ng/mL, • Biomarkers combined w/ MC at Dx of HCC Conclusion: Using both biomarkers and the Milan criteria may be better than using the MC alone in optimizing the decision of liver transplantation eligibility. Chaiteerakij J et al Liver Transpl. 2015 May ; 21(5): 599–606.

  15. Case 1 • Patient underwent LDLT 11/08/17 after Y90 to new lesion • AFP pre-op 18.7 • A.  Liver, excision: Hepatic cellular carcinomas arising in a cirrhotic liver (see note). • B.  Portal vein, resection: Segment of portal vein, no tumor seen. • C.  Bile duct, resection: Fibroadipose tissue and nerves with yttrium beads. • Note: There are three separate tumors, each measuring 1.7, 1.7 and 1.5 cm in greatest dimension. The two tumors located in the left lobe show extensive necrosis (90-95%). The other tumor nodule seen at the hilum adjacent to the portal vein is confined to the large bile duct and is completely viable, showing grade 3 differentiation and contains theraspheres. No vascular invasion is seen. The portal vein and bile duct margins are unremarkable. In all three tumors and adjacent liver, theraspheres are identified.

  16. Case 1 • Would immunotherapy have been a consideration? • If so, when? • If given immunotherapy, would transplant ever be considered an option?

  17. Immune Therapy Post OLT • Recurrent HCC 2 yrs. Post OLT • Disease progression with Sor • 1 dose Nivo • 1 wk. later rapid progressive liver dysfunction • Liver bx: severe ACR, no response to steroids • Pt. died 35 d after Nivo • Review of literature • 29 cases of solid organ treated with checkpoint inhibitor • Graft loss 36% in OLT, 54% CRT Gassman D et al. Transplantation Direct 2018;4:1-7

  18. Case 1 • Patient HCV treated post OLT with SVR • 1 episode of moderate acute cellular rejection 1 month post OLT • Imaging, MRI and Chest CT without evidence of recurrence • AFP wnl post OLT • Transitioned to everolimus once HCV treatment completed in 04/18

  19. Case 2 • 68 y/o male with no known prior hx of liver disease with a history of lung cancer s/p resection 03/2014 (T1; KRAS+, GR 2-3) • Noted to have a solitary liver lesion, 2.8 cm noted on surveillance chest CT in 08/15 • Triphasic CT abdomen • 2.8 x 2.5 cm arterially enhancing lesion which demonstrates washout on the venous phase. There is a questionable thin rim of hyperenhancement on the venous phase. This lesion is new compared to the prior outside CT abdomen/pelvis dated 3/5/2014 • Should a biopsy be considered of lesion?

  20. Case 2 • Patient diagnosed with HCV, genotype 1A and alpha 1 AT MZ • Bx of liver lesion moderately differentiated HCC • Labs: 09/15: INR 1.1, Plt 416,000 (repeat 270,000), bilirubin 0.6, albumin 3.6, AST 27, ALT 48, creatinine 0.75, AFP 121 (MELD = 7) • HVPG 7 mmHg • What would you consider for therapy?

  21. Case 2 FLR 32%

  22. Case 2 • CT read: Mildly prominent paraesophageal and right cardiophrenic lymph nodes are stable compared to the prior CT from 3/5/2014.  Multiple enlarged periportal, celiac axis, and gastrohepatic nodes are also grossly stable. The largest node near the portahepatis measures 2.7 x 1.5 cm, previously 3.0 x 1.6 cm • Does this effect treatment decision? • He was treated with LOBAR Y90

  23. Case 2 • Scan post-Y90 on 10/26/15 showing good treatment response • AFP declined to 14

  24. Case 2 Right lobe resection 12/15 Pathology: • Liver, right lobe, right hepatic lobectomy: • Hepatocellular carcinoma with 95% necrosis containing Yttrium beads (see note). The necrotic tumor measures approximately 1.4 cm in greatest dimension. No vascular invasion is seen.   • A separate nodule of hepatocellular carcinoma, grade 3, measuring 5 mm in greatest dimension, and with an occasional Yttrium bead. • Adjacent liver with cirrhosis. • Margins of resection are unremarkable.

  25. Case 2 • Any recommendations regarding follow up? • Is the patient a future OLT candidate if has recurrence? • Due to grade 3 tumor seen? • Ab initio OLT? • Treat HCV? • If so when? • HCV treated with SVR post resection • Completed 24 weeks of Viekira + riba 400 BID on 07/25/16

  26. Case 2 • Repeat CT scan 18 months post resection (06/17) • New lung lesion and para tracheal LN + Lung cancer: treated with XRT and chemotherapy • New 1.2 cm liver lesion along surgical margin treated with RFA • Consideration for systemic therapy? • 6 months later (12/17) noted to have abdominal wall met, 3.4 cm c/w HCC, treated with cryoablation • Started on Durvalumab 10/17 for lung cancer for planned 1 year treatment course

  27. Case 2 • Scan 07/18 • There is a new, nonspecific 7 mm hypodensity in the liver.  The ablation cavity in the liver is slightly smaller measuring 24 mm, previously 26 mm.The soft tissue thickening in the right lateral chest wall from prior ablation is smaller measuring 17 mm in thickness, previously 20 mm.A portahepatis lymph node measuring 14 mm previously measured 13 mm.  Other upper abdominal lymph nodes are stable.

  28. Scan 11 mo. on PD1 (10/18)Abdominal pain & fever Biopsy performed

  29. Case 2 1.  There is a new liver mass measuring 81 mm.2.  Lymph nodes in the portahepatis measuring up to 31 mm have enlarged, previously 14 mm.3.  Multiple subcentimeter lymph nodes in the mediastinum have enlarged.4.  There is new free fluid in the pelvis.5.  Solid nodules in the right lung measuring up to 9 mm have enlarged.

  30. Case 2 • Diagnostic Category Positive for Malignancy • Final Diagnosis Hepatocellular carcinoma, grade 3 (see note) • AFP 317, bilirubin 0.9, AST 67, ALT 59, AP 161, albumin 3.7, INR 1.4

  31. Progression True Progression Hyperprogression Pseudoprogression VS. VS.

  32. Example of Hyperprogressive Disease (HPD) Champiat S et al. Clin Cancer Research 2017

  33. Observations Made • 9% met criteria for HPD • HPD was not associated baseline tumor burden, # or type of prior tumor therapies • HPD was equally associated with PD-1 and PD-L1 blockers • HPD was associated equally across tumor types • HPD was associated with: • Older age • Worse OS • REF TGR inversely correlated with response to PD-1/PD-L1: slower growing tumors less likely to respond Champiat S et al. Clin Cancer Research 2017

  34. Case 2 • What would you do next?

  35. Case 2 • He was started on Lenvatinib 12mg on 11/08/18 • At 2 week follow up, patient tolerating well but had lost 16 lbs, and was now 60.3 kg • Lower dose at this time?

  36. Case 2 • CT 12/05/18 (1 month after Levatinib start) 1.  Large liver mass measures smaller. It is more heterogeneous and conspicuous likely related to new areas of necrosis.2.  There are a few new hypodense liver lesions that measure under a centimeter. As noted above, it is uncertain if these are new sites of tumor or if they are sites of tumor that were not clearly seen previously but are now conspicuous due to treatment response/partial necrosis. These can be reassessed on follow-up imaging.3.  Lymphadenopathy within the chest and in the upper abdomen is redemonstrated. Some of the nodes are smaller. Some of the nodes demonstrate new heterogeneity likely reflecting partial necrosis.4.  The 3 enlarging right lung nodules on the prior study have all at least slightly decreased in size. Semisolid nodule in the superior aspect of the right lung is unchanged. Continue current therapy?

  37. Case 2 • CT 01/30/19 (3 months after Levatinib start) 1.  The large infiltrative mass in the left hepatic lobe and multiple small satellite hepatic lesions have significantly decreased in size.2.  Necrotic upper abdominal adenopathy has also decreased in size.3.  Stable postsurgical changes of right lower lobectomy and right paramediastinalpostradiation fibrosis.4.  Two low-attenuation pancreatic lesions are stable to slightly decreased in size.5.  Stable mixed groundglass and solid right upper lobe 1.6 cm nodule. Recommend continued attention on follow-up imaging. There are no new or enlarging pulmonary nodules. Continue current therapy?

  38. Case 2 • CT 04/17/19 (5 months after Levatinib start) 1.  Soft tissue nodules along the right lateral chest wall, just superior to the right hemidiaphragm, have slightly increased in size.  The larger of these measures 31 mm, previously 28 mm.2.  The ill-defined hepatic mass is slightly smaller measuring 47 x 43 mm, previously 51 x 48 mm in the same dimensions on the prior study.3.  Enlarged lymph nodes in the upper abdomen have slightly decreased in size.  One lymph node in the gastrohepatic ligament region is larger, but has undergone central necrosis in the interval.4.  There is a new, small amount of free fluid in the pelvis, likely secondary to cirrhosis.  5.  There has been a prior right lower lobectomy.  There is stable radiation fibrosis in the perihilar right lung. Continue current therapy?

  39. Case 2 • CT 08/07/19 (9 months after Levatinib start) 1.  Stable postsurgical changes of right lower lobectomy, right paramediastinal fibrosis, and pulmonary nodules.2.  Improvement of hepatic lesions.3.  Improvement of right anterior lateral upper abdominal nodules although there is increased periportal and perigastricadenopathy. Complex cystic necrotic lymph node adjacent to portal measures 5.5 x 4.1 cm compared to previous of 4.8 x 2.7 cm.  Left abdominal perigastric necrotic lymph node 3.5 x 2.7 cm compared to previous of 2 x 1.6 cm. Continue current therapy?

  40. Case 3

  41. Case 2 • Patient started on Cabozantinib 40mg

  42. ThankYou

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