Kidney cancers
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Comprehensive overview of Kidney Cancer: staging, diagnosis and treatment

Comprehensive overview of Kidney Cancer: staging, diagnosis and treatment

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Kidney cancers Kidney cancers Presentation Transcript

  • 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 RCC are clear cell tumors.¡ Risk factors: § Smoking § Obesity § Von Hippel-Lindau disease (VHL): ▪ Mutations of VHL gene predisposed to clear RCC
  • ¡ 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
  • ¡ Mass (clinically in the flank, incidental by US)¡ Hematuria¡ Flank pain
  • ¡ 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??
  • ¡ 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
  • Tis/0 T1 T2 T3 T4 M1=IVN0 0 I II III IV 96% 82%N1 III 64% 23%N2 IV
  • ¡ 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
  • ¡ 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)
  • ¡ Feasibility¡ Very early tumors (T1)¡ If RN renders patient anephric: § Tumor in a solitary kidney § Poor contralateral kidney functions § Bilateral tumors (VHL)
  • 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 for LN+ and SM+: § No benefit
  • ¡ Elderly¡ Poor general condition¡ Actions: § Surveillance § Ablation ▪ Radiofrequancy ▪ cryo
  • ¡ 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
  • ¡ 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.
  • ¡ Memorial Sloan-Kettering Cancer Center (MSKCC) and¡ Cleveland Clinic Foundation (CCF)
  • ¡ Indicated in: § Metastatic § Irresectable § recurrent¡ Agents: § Cytokines: ▪ IL-2: high-dose produce high RR ▪ INF § Targeted therapy: ▪ Sunitinib ▪ Sorafenib ▪ Temsirolimus ▪ Bevacizumab ▪ Everolimus
  • ¡ 1st line: § Single agents: ▪ Sunitinb: good and intermediate risk ▪ Temsirolimus: poor risk ▪ Sorafenib: selected patients § Combination: ▪ Bevacizumab+ INF ▪ Sorafenib+INF¡ 2nd line ▪ Everolimus ▪ Others
  • ¡ 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
  • 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
  • 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.
  • ¡ 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.
  • ¡ 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
  • ¡ + 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$/Month
  • ¡ 25 mg IV weekly over 30- 60 min¡ Premedication with antihistamine¡ 1st line in RCC with >=3 poor prognostic criteria¡ till progression or unacceptable toxicity¡ inhibit mammalian Target of Rapamycin (mTOR) protein¡ Cost: 7500$/month
  • ¡ The most common grade 3 or 4 AE include: § rash, § stomatitis, § pain, § infection, § peripheral edema, § Thrombocytopenia and neutropenia § hyperlipidemia, hypercholesteremia, and hyperglycemia
  • ¡ Oral multikinase inhibitor § PDGFR § VEGFR¡ Inhibits tumor cell proliferation and angiogenesis Ahmed Zeeneldin 52
  • • Oral• 400 mg BID continuously• Can be increased to 600 mg BID• Cost: 5000 $/Month• PFS: • Sorafenib vs INF: • 5.7 m vs 5.6m 53
  • ¡ Anti-VEFG-A MAB¡ IV 10 mg q 2weeks¡ Costs: 7500$/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 8%), § fatigue(35% v 28%), § proteinuria(13% v 0%).
  • ¡ 10 mg tablets¡ 2nd line after failure of sunitinib or sorafenib
  • ¡ Best: Temsirolimus¡ Next: Sunitinib, Sorafenib¡ Third: chemotherapy with mild activity § Capecitabine § Gem+/- 5-FU § Doxorubicin-based