1. Renal Cell Carcinoma: cytoreduction,embolization and targeted therapy
PhD. Varujan H.Shahsuvaryan
MD. Nairi R. Melkonyan
National center of Oncology, Yerevan, Armenia,2018

2. Renal Cell Carcinoma 2-3% of all cancers
Highest incidence in Western countries
The incidence increased by about 2%
1,5:1 male predominance
Peak incidence between 60 and 70 years
Aetiological factors: smoking,obesity,hypertension, family hystory

3. A model of smoking epidemic (WHO)
Lopez AD, Collishaw NE, Piha T

4. RCC and Aremnia (2008-2017 dynamics)
Observed years
Dynamics
2008 year
2017 year
New cases
Deaths
Neglect cases
RCC
181 91 64
203
107 67
+22
+16 +3
Observed years
Dynamics
2008 year
2017year
Morb.
Mort.
Negl.(%)
Negl. (%)
RCC
5,8
2,9
35,3
6,7
3,5
33,0
+0.9
+0.6
-2,3%

5. EAU 2018 Guidelines on RCC

6. Prognostic models

7. Memorial Sloan-Kettering Cancer Center (MSKCC/Motzer) Score
Time from diagnosis to systemic treatment <1 year
Measured ~1 month after stopping anticoagulation
Hemoglobin < Lower Limit of Normal
Men (Normal): g/dL
Women (Normal): g/dL
Calcium >10mg/dL (>2.5 mmol/L)
LDH > 1.5x Upper Limit of Normal
Normal: 140 U/L
Performance status <80% (Karnofsky)
______________________________________________________________
Favourable (low) risk - no risk factors;
Intermediate risk - one or two risk factors; 
Poor (high) risk - three to six risk factors.

8. The International Metastatic Renal Cancer Database Consortium (IMDC) risk model
Karnofsky performance status < 80%
Time from diagnosis to treatment < 12 months
Haemoglobin < Lower limit of laboratory reference range
Corrected serum calcium > 10.0 mg/dL (2.4 mmol/L)
Absolute neutrophil count (neutrophilia) > upper limit of normal
Platelets (thrombocytosis)> upper limit of normal
Favorable-risk group - no poor prognostic factors
Intermediate-risk group – 1 or 2 prognostic factors
Poor-risk group - more than two prognostic factors

9. Cytoreductive nephrectomy

10. Cytoreductive nephrectomy

11. CNX improves IFN response!!!
Cytoreductive Nx+IFN
SWOG
EORTC
SWOG – southwest oncology group
EORTC – European Oganization for research and treatment of cancer
CNX improves IFN response!!!

12. Defferred cytoreductive nephrectomy

13. RCC metastasectomy
Around 20% and 30% of renal cell carcinomas show metastases at the time of diagnosis or develop metastases after radical nephrectomy. In renal cell carcinoma, metastasectomy may be performed with curative intent; compared with systemic therapy alone, it is associated with a survival advantage in patients with lung and liver metastases and leads to 5-year-survival rates of 40% to 50% and 62% respectively (evidence level IIB).

14. Conclusion

15. (metal osteosynthesis)
A clinical case
A 62 y.o. male
Left-sided flank pain (2 months),
gross hematuria (1 week), anemia (92 g/L)
Bone and lung metastases
4 years ago – renal selective embolization
2 years ago – pathologic fracture of the arm
(metal osteosynthesis)
Targeted therapy with Sunitinib.
National center of Oncology, Yerevan, Armenia

16. Presurgical CT
National center of Oncology, Yerevan, Armenia

17. Diagnosis Left-sided RCC, T3N1M1 (intermediate risk), macrohematuria.
Treatment
Targeted theraphy
Embolization
Cytoreductive nephrectomy , (ONC Armenia)
Continuation of the targeted theraphy with Sunitinib
Good QOL!!!

18. Embolization

19. Hystory
In 1969, Lalli, using synthetic particles as an embolic agent in a canine model, was the first to describe this concept.
In 1973, Almgard et al.,Stockholm, Sweden, reported the application of renal embolic infarction to patients with metastatic neoplastic disease.

20. EMBOLIZATION TECHNIQUE
The right common femoral artery approach is commonly used.
Access is gained via a 22-gauge micropuncture system.
5Fr cobra catheter.
A Bentson wire (Cook, Bloomington, IN).
A short 5Fr sheath is then placed and secured to the skin, and a 5Fr flush catheter advanced to the level of T11.
An aortogram is performed!!!

21. Aortogram
To evaluate renal and accessory renal arteries (in ~ 25% of cases there is a renal accessory artery, which is usually inferior to the main and supplies the inferior pole)
Or possible parasitized vessels
A subtraction run at 5 to 6 mL/s is sufficient to opacify the renal vessels with standard nonionic contrast
Two projections are obtained to fully evaluate the entire vascular tree

22. Renal arteriography
The renal arteries usually arise at the L1-L2 level
The feeding vessel can be selectively catheterized and embolized with a 4Fr catheter or using a coaxial microcatheter system

23. Embolic agents
Different embolic agents were used, such as Gelfoam® absorbent gelatin sponge (Pfizer, USA), polyvinylalcohol (PVA) microparticles, Contour® (Boston Scientific, USA), Coils (Boston Scientific, USA), Embosphere® embospheres ), Onyx® (eV3-MTI, Irvine, CA, USA), N-butyl-2 cyanoacrylate NBCA® (TruFill, Cordis, Miami Lakes, Fl. Glubran 2, Gem, Viareggio, Lucca, Italy) or absolute alcohol

24. Literature

25. Complications The mean complication rate was 5-10% Mortality: 2-3%
Postembolization syndrome: 36-92%
Flank acute pain, fever up to 39OC, nosea and vomiting,decreased dyuresis
[Schwartz M. et al., Serafin Z. et al.]
May occure starting from 3rd day to 3rd week
No need for specific treatment (symptomatic treatment)
Arterial hypertension: 3-5%/ arterial hypotension: 0.5%
Pseudoaneurysm (place of access): 0,2-2,2%
Others: embolic agent reflux and migration (S. Wallace et al.), colon infarction, pulmonary arterial thromboembolism (Vogel et al., Yurin et al.), renal failure, renal abscess, heart attack and failure...

26. A clinical case Anamnesis A 61 y.o. woman
With right-sided blunt flank pain
(almost 5 months ) and massive gross hematuria (almost а month)
She took hemostatics, which had been unusefull
National center of Oncology, Yerevan, Armenia

27. Laboratory findings Electrolytes Coagulogramm
Blood analyses: HGB 80 g/L RBC 2,2 * 106 /uL HCT 30,5 % WBC 8,68* 103 /uL NEUT% 83,0 % PLT 339* 103 /uL ESR 56 mm/h
Blood byochemical analyse
Creatininе – 83 mkmol/l
Alkaline phosphatase - 57,8 U/l
(norm.: U/L)
LDH 155,9 U/l
(norm.: 140U/L)
Electrolytes
Ca ,6mmol/l
(norm.: 2,15-2,57mmol/l)
Coagulogramm
Normal
National center of Oncology, Yerevan, Armenia

28. Contrast-enhanced computed tomography (CT)

29. Computed tomography (Thoracic)

30. Diagnosis Right-sided renal-cell carcinoma, T3aN1M1, Stage IV (Poor risk), macrohematuria. Treatment Embolization Targeted theraphy Cytoreductive nephrectomy ?

31. Video

32. Post surgical CT

33. Pre- and postembolization CT

34. Conclusion for embolization for mRCC
In patients unfit for surgery
With non-resectable disease
Can control symptoms, including visible haematuria or flank pain

35. Monoclonal antibody against circulating VEGF
Systemic therapy
Targeted therapies
Tyrosine kinase inhibitors
Sorafenib
Sunitinib
Pazopanib
Axitinib
Cabozantinib
Lenvatinib
Tivozanib
Monoclonal antibody against circulating VEGF
Bevacizumab monotherapy and bevacizumab plus IFN-α
mTOR inhibitors
Temsirolimus
Everolimus
Chemotherapy
In sarcomatoid and rapidly progressive disease
Immunotherapy Immune checkpoint blockade
Nivolumab and Ipilimumab (CheckMate 214 NCT ) – first– line
Nivolumab (CheckMate 025) – second – line
Atezolizumab (Immotion 150) – second line

36. Hystory

37. Targeted therapy

38. Mechanism

39. EAU 2018 Guidelines on RCC

40. Answers - in the near future ....!
The search continues ...
Perisurgical therapy .... ?
Adjuvant therapy …. ?
Resistance therapy strategy for primary resistance ....?
Combined therapy …. ?
Answers - in the near future ....!

41. Thank you!!!