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Ahmed ZeeneldinAssociate professor of Medical Oncology/Hematology                         NCI                        2010
CT e Contrast:NB: Contrastnephropathy and theuse of N-acetylcysteine
Typical renal cell carcinoma.CT scan obtained beforecontrast enhancement
NON-ENHANCED   ENHANCED
¡   Contrast-enhanced MRI    (renal cell carcinoma)
¡   2-3 % of all malignancies¡   58 000 case & 13 000 deaths¡   5-y OS : 70%¡   90% of renal tumors are RCC, and¡   85% of...
¡   Tumor grade¡   Stage:    § Tumor    § LN    § Mets¡   Risk stratification: MSKCC    1.   LDH > 1.5 ULN    2.   HB < LL...
¡   Mass (clinically in the flank, incidental by US)¡   Hematuria¡   Flank pain
¡   H&P¡   Lab:    §   CBC    §   KFT & urine    §   LFT    §   Others: calcium, LDH, coagulation profile¡   Imaging:    §...
¡   T1: limited to kidney <= 7cm    § T1a: <=4cm    § T1b: >4-7 cm¡   T2: limited to kidney > 7cm¡   T3:    § T3a: adrenal...
Tis/0 T1    T2 T3      T4   M1=IVN0    0     I    II   III         IV          96% 82%N1         III        64%        23%...
¡   Modalities:    § Surgery    § Systemic therapy:       ▪ Cytokines       ▪ Targeted therapy       ▪ Not including Chemo...
¡   Only curative Tx¡   Localized (I-III; T1-3, N0-1)¡   Types:    § radical nephrectomy and    § nephron-sparing surgery¡...
¡   Feasibility¡   Very early tumors (T1)¡   If RN renders patient anephric:    § Tumor in a solitary kidney    § Poor con...
NO ROLEObservation:Low risk for Recurrence:High risk: LN+ large tumors, +ve Margin
¡   RCT of    § INF and IL-2 vs. observation    § Completely resected tumors¡   No DFS advantage¡   No OS advantage¡   RT ...
¡   Elderly¡   Poor general condition¡   Actions:    § Surveillance    § Ablation      ▪ Radiofrequancy      ▪ cryo
¡   Synchronous or metachronous mets¡   Surgery if possible    § for 1ry: complete or incomplete (cytoreduction)    § 2ry ...
¡   Resectable Stage IV RCC                             INF alone   INF + Surgery    MOS (P<0.002)              7.8 m     ...
¡   Memorial Sloan-Kettering Cancer Center (MSKCC) and¡   Cleveland Clinic Foundation (CCF)
¡   Indicated in:    § Metastatic    § Irresectable    § recurrent¡   Agents:    § Cytokines:      ▪ IL-2: high-dose produ...
¡   1st line:    § Single agents:      ▪ Sunitinb: good and intermediate risk      ▪ Temsirolimus: poor risk      ▪ Sorafe...
¡   VHL = von Hippel–Lindau protein;¡   HIF = hypoxia-inducible factor,¡   TGF-α = transforming growth factor α;¡   VEGF =...
Regimen             Setting               Therapy                Options1st line   MSKCC risk:              Sunitinib     ...
Fig. 1 Biologic agents and their targets in metastatic renal cell cancer.VHL = von Hippel-Lindau; HIF = hypoxia-inducible ...
¡   Consequences of mutation or inactivation of the von Hippel Lindau    (VHL) gene.¡   VHL normally encodes a protein (p-...
¡   Oral multi-tyrosine kinase    inhibitor    §   PDGF    §    VEGF-R    §   Stem cell factor receptor (c-KIT)    §   FMS...
¡   + PFS by 6 m    § (from 5m to 11 m)¡   + OS by 4 m    § (from 22 m to 26m)¡   AE:    § HTN, HFS, diarrhea, +AST/ALT,  ...
¡   25 mg IV weekly over 30-    60 min¡   Premedication with    antihistamine¡   1st line in RCC with >=3    poor prognost...
¡   The most common grade 3 or 4 AE include:    § rash,    § stomatitis,    § pain,    § infection,    § peripheral edema,...
¡   Oral multikinase    inhibitor    § PDGFR    § VEGFR¡   Inhibits tumor    cell proliferation    and angiogenesis       ...
•   Oral•   400 mg BID continuously•   Can be increased to 600 mg    BID•   Cost: 5000 $/Month•   PFS:    • Sorafenib vs I...
¡   Anti-VEFG-A MAB¡   IV 10 mg q 2weeks¡   Costs: 7500$/month
¡   PFS: 8.5 m vs 5.2 m¡   OS: 18m vs 17m¡   RR: 25% vs 13%¡   Grade 3 AE:    § hypertension(9% v 0%),    § anorexia(17% v...
¡   10 mg tablets¡   2nd line after failure of sunitinib or sorafenib
¡   Best: Temsirolimus¡   Next: Sunitinib, Sorafenib¡   Third: chemotherapy with mild activity    § Capecitabine    § Gem+...
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
Kidney cancers
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Kidney cancers

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Comprehensive overview of Kidney Cancer: staging, diagnosis and treatment

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Transcript of "Kidney cancers"

  1. 1. Ahmed ZeeneldinAssociate professor of Medical Oncology/Hematology NCI 2010
  2. 2. CT e Contrast:NB: Contrastnephropathy and theuse of N-acetylcysteine
  3. 3. Typical renal cell carcinoma.CT scan obtained beforecontrast enhancement
  4. 4. NON-ENHANCED ENHANCED
  5. 5. ¡ Contrast-enhanced MRI (renal cell carcinoma)
  6. 6. ¡ 2-3 % of all malignancies¡ 58 000 case & 13 000 deaths¡ 5-y OS : 70%¡ 90% of renal tumors are RCC, and¡ 85% of RCC are clear cell tumors.¡ Risk factors: § Smoking § Obesity § Von Hippel-Lindau disease (VHL): ▪ Mutations of VHL gene predisposed to clear RCC
  7. 7. ¡ Tumor grade¡ Stage: § Tumor § LN § Mets¡ Risk stratification: MSKCC 1. LDH > 1.5 ULN 2. HB < LLN 3. Corrected serum calcium level > 10 mg/dl (2.5 mmol/liter) 4. Interval of less than a year from original diagnosis to the start of systemic therapy 5. Karnofsky performance score <= 70 6. >= 2 sites of organ metastasis
  8. 8. ¡ Mass (clinically in the flank, incidental by US)¡ Hematuria¡ Flank pain
  9. 9. ¡ H&P¡ Lab: § CBC § KFT & urine § LFT § Others: calcium, LDH, coagulation profile¡ Imaging: § CT with contrast: CAP § MRI if we cannot use CT e contrast : CAP § Others if indicated: MRI/CT brain, Bone scan § PET??
  10. 10. ¡ T1: limited to kidney <= 7cm § T1a: <=4cm § T1b: >4-7 cm¡ T2: limited to kidney > 7cm¡ T3: § T3a: adrenals § T3b RV or infradiaph IVC § T3c: perinephric fat, limited to Gerota’s fascia¡ T4: beyond Gerota’s fascia¡ N1: one LN¡ N2: >one LN¡ M1: mets
  11. 11. Tis/0 T1 T2 T3 T4 M1=IVN0 0 I II III IV 96% 82%N1 III 64% 23%N2 IV
  12. 12. ¡ Modalities: § Surgery § Systemic therapy: ▪ Cytokines ▪ Targeted therapy ▪ Not including Chemox § RT: limited role¡ Treatment by stage: § Stage I-III: ▪ Surgery: RN, NSS ▪ No adjuvant Tx: no RT no systemic Tx § Stage: IV ▪ Surgery if possible for 1ry and 2ry (metastatectomy) ▪ Systemic therapy ▪ RT limited role
  13. 13. ¡ Only curative Tx¡ Localized (I-III; T1-3, N0-1)¡ Types: § radical nephrectomy and § nephron-sparing surgery¡ Removes: § Tumor + SM +/- kidney § Peri-renal fat § Fascia § Regional LN (prognostic) § Ipsilateral adrenal (upper pole tunors)
  14. 14. ¡ Feasibility¡ Very early tumors (T1)¡ If RN renders patient anephric: § Tumor in a solitary kidney § Poor contralateral kidney functions § Bilateral tumors (VHL)
  15. 15. NO ROLEObservation:Low risk for Recurrence:High risk: LN+ large tumors, +ve Margin
  16. 16. ¡ RCT of § INF and IL-2 vs. observation § Completely resected tumors¡ No DFS advantage¡ No OS advantage¡ RT for LN+ and SM+: § No benefit
  17. 17. ¡ Elderly¡ Poor general condition¡ Actions: § Surveillance § Ablation ▪ Radiofrequancy ▪ cryo
  18. 18. ¡ Synchronous or metachronous mets¡ Surgery if possible § for 1ry: complete or incomplete (cytoreduction) § 2ry (lung, bone, brain metastatectomy) § Simultaneously or sequentially¡ RT can be used for irresectable or post resection in bone or brain¡ Systemic therapy: INF, IL-2, targeted therapy
  19. 19. ¡ Resectable Stage IV RCC INF alone INF + Surgery MOS (P<0.002) 7.8 m 13.6 m¡ RR of death decreased by 30%¡ Independent of § patient performance status, § the site of metastases and § the presence of measurable disease.
  20. 20. ¡ Memorial Sloan-Kettering Cancer Center (MSKCC) and¡ Cleveland Clinic Foundation (CCF)
  21. 21. ¡ Indicated in: § Metastatic § Irresectable § recurrent¡ Agents: § Cytokines: ▪ IL-2: high-dose produce high RR ▪ INF § Targeted therapy: ▪ Sunitinib ▪ Sorafenib ▪ Temsirolimus ▪ Bevacizumab ▪ Everolimus
  22. 22. ¡ 1st line: § Single agents: ▪ Sunitinb: good and intermediate risk ▪ Temsirolimus: poor risk ▪ Sorafenib: selected patients § Combination: ▪ Bevacizumab+ INF ▪ Sorafenib+INF¡ 2nd line ▪ Everolimus ▪ Others
  23. 23. ¡ VHL = von Hippel–Lindau protein;¡ HIF = hypoxia-inducible factor,¡ TGF-α = transforming growth factor α;¡ VEGF = vascular endothelial growth factor A;¡ PDGFβ = platelet-derived growth factor β;¡ EGFR = epidermal growth factor receptor,¡ VEGFR2 = VEGF receptor 2;¡ PDGFRβ = PDGF receptor β;¡ PTEN = phosphatase and tensin homologue;¡ TSC1 and TSC2 = tuberous sclerosis complex 1 and 2;¡ FKBP12 = FK506-binding protein 12 kD;¡ mTOR = mammalian target of rapamycin complex 1 kinase;¡ eIF4E = eukaryotic translation initiation factor 4E;¡ S6K = S6 kinase
  24. 24. Regimen Setting Therapy Options1st line MSKCC risk: Sunitinib High-dose IL-2 Good or intermediate bevacizumab + IFN-α MSKCC risk: Poor Temsirolimus Sunitinib2nd line Cytokine-refractory Sorafenib Sunitinib bevacizumab Refractory to VEGF/VEGFR Sequential TKIs or Everolimus or mTOR inhibitors VEGF inhibitor
  25. 25. Fig. 1 Biologic agents and their targets in metastatic renal cell cancer.VHL = von Hippel-Lindau; HIF = hypoxia-inducible factor; mTOR = mammaliantarget of rapamycin; VEGF = vascular endothelial growth factor; PDGF = platelet-derived growth factor; TGF-α = tumour growth factor-alfa; VEGFR = vascularendothelial growth factor receptor; PDGFR = platelet-derived growth factorreceptor; EGFR = epidermal growth factor; HGF = hepatocyte growth factor.
  26. 26. ¡ Consequences of mutation or inactivation of the von Hippel Lindau (VHL) gene.¡ VHL normally encodes a protein (p-VHL) that targets hypoxia- inducible factor (HIF) for proteolysis.¡ As a result of VHL inactivation, a defective p-VHL is produced and HIF is up-regulated, translocates to the nucleus, and results in the transcription of several genes involved in angiogenesis and tumor growth. These genes include vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-α, basic fibroblast growth factor (bFGF), carbonic anhydrase IX (CA IX) or G250, erythropoietin (EPO), and others.¡ OH indicates hydroxyl group;¡ Ub, ubiquitin;¡ Glut-1, glucose transporter 1;¡ PAI-1, plasminogen activator inhibitor 1.
  27. 27. ¡ Oral multi-tyrosine kinase inhibitor § PDGF § VEGF-R § Stem cell factor receptor (c-KIT) § FMS-like tyrosine kinase (Flt3), § colony stimulating factor (CSF-1R), § The neurotrophic factor receptor (RET)¡ Inhibits angiogenesis and cell proliferation.¡ Indication: advanced RCC § 1st line § Met/Rec or irresectable
  28. 28. ¡ + PFS by 6 m § (from 5m to 11 m)¡ + OS by 4 m § (from 22 m to 26m)¡ AE: § HTN, HFS, diarrhea, +AST/ALT, - plt, -ANC¡ Dose: 50 mg daily x 6 weeks and 2 weeks rest¡ Cost : 10500$/Month
  29. 29. ¡ 25 mg IV weekly over 30- 60 min¡ Premedication with antihistamine¡ 1st line in RCC with >=3 poor prognostic criteria¡ till progression or unacceptable toxicity¡ inhibit mammalian Target of Rapamycin (mTOR) protein¡ Cost: 7500$/month
  30. 30. ¡ The most common grade 3 or 4 AE include: § rash, § stomatitis, § pain, § infection, § peripheral edema, § Thrombocytopenia and neutropenia § hyperlipidemia, hypercholesteremia, and hyperglycemia
  31. 31. ¡ Oral multikinase inhibitor § PDGFR § VEGFR¡ Inhibits tumor cell proliferation and angiogenesis Ahmed Zeeneldin 52
  32. 32. • Oral• 400 mg BID continuously• Can be increased to 600 mg BID• Cost: 5000 $/Month• PFS: • Sorafenib vs INF: • 5.7 m vs 5.6m 53
  33. 33. ¡ Anti-VEFG-A MAB¡ IV 10 mg q 2weeks¡ Costs: 7500$/month
  34. 34. ¡ PFS: 8.5 m vs 5.2 m¡ OS: 18m vs 17m¡ RR: 25% vs 13%¡ Grade 3 AE: § hypertension(9% v 0%), § anorexia(17% v 8%), § fatigue(35% v 28%), § proteinuria(13% v 0%).
  35. 35. ¡ 10 mg tablets¡ 2nd line after failure of sunitinib or sorafenib
  36. 36. ¡ Best: Temsirolimus¡ Next: Sunitinib, Sorafenib¡ Third: chemotherapy with mild activity § Capecitabine § Gem+/- 5-FU § Doxorubicin-based
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