1.Presented By:Dr. VandanaDept. of RadiotherapyCSMMU, Lucknow1

2. Anatomy of Kidney pair of organs located in the abdominal cavity on either side of the spine in a retroperitoneal position. Adrenal glands rest on top of each kidney Approx. at vertebral level T12 to L3, right kidney being slightly lower than the left. Long axis of kidney is directed downward and laterally Approx. 1114 cm in length, 6 cm wide and 4 cm thick weighs around 150 gm in males & 135 gm in females. Mobile Organ, move vertically within retroperitoneum 0.9 cm to 1.3 cm., as much as 4 cm during normal respiration 2 3. The kidney is surrounded by tough fibroustissue, the renal capsule, which is itselfsurrounded by perinephric fat, renal fascia(of Gerota) and paranephric fat. parenchyma, of the kidney is divided intotwo major structures: renal cortex andrenal medulla Fig: Anterior relations of kidneys Fig: Posterior relations of kidneys 3 4. Blood Supply Approx. 20% of the cardiac output . From renal arteries, left and right, which branch directly from the abdominal aorta. renal vein emerges from hilum and drains into the inferior vena cava. Lymph Drainage : to the lateral aortic lymph nodes around the origin of the renalartery. Nerve Supply: Through renal sympathetic plexus (T10 L1) fibres, mainly vasomotor. Afferent nerves T10 to T12 thoracic nerves. Functions Excretion of wastes, Acid-base homeostasis, Osmolality regulation, Blood pressure regulation and Hormone secretion 4 5. Renal Tumors 51,000 cases diagnosed and more than 12,900 deaths annually in the US Account for approx. 3% of adult malignancy 5 6. Renal tumors Benign Oncocytoma Papillary adenoma Angiomyolipoma Malignant Renal Cell Carcinoma (Adenocarcinoma of Kidney)6 7. Renal Cell Carcinoma First described by Konig in 1826. In 1883 Grawitz, noted the fatty content of cancer cellssimilar to that of adrenal cells. All these tumors arise from Renal tubular epithelium. accounts for 8085% of kidney cancer 2% to 4% increase in incidence per year 7 8. Epidemiology Male predominance (1.6:1.0 M:F) Highest incidence between age 50-70-Median age of diagnosis is 66 years-Median age of death 70 years Majority of RCC occurs sporadically Highest incidence in Scandinavia and North America, lowest in Africa8 9. Risk Factors Tobacco smoking contributes to 24-30% of RCC cases- Tobacco results in a 2-fold increased risk Environmental: Cadmium, thorium-di-oxide, petroleum and phenacetin analgesics. Occupational: leather tanners, shoe workers, asbestos workers. Hormonal: diethylistillbestrol, Obesity, HTN 35% - 47% pt on long term dialysis develop Acquiredpolycystic kidney disease, out of which 5.8% developsRenal cancer. 9 10. RCC is not one disease It is made up of no. of different types of cancers with different histology, different clinical courses and caused by different gene.TypeClear cellPapillary type 1 Papillary type 2Chromophobe OncocytomaIncidence (%)75%5%10%5% 5%Associated VHLc-MetFH BHDBHD mutations A sarcomatoid variant represents1% to 6% of renal cell carcinoma and these tumors are associated with a significantly poorer prognosis. BHD=Birt-Hogg-Dub; FH=fumarate hydratase; VHL=von Hippel-Lindau. 10 11. Hereditary Renal Cancer Syndromes SyndromeChromosomeRenalOther Manifestations Location Manifestations(Gene)Von Hippel-3p25 Clear cell renal Retinal and central nervous systemLindau (VHL) VHLcarcinoma: solid hemangioblastomas; pheochromocytomas;and/or cystic, pancreatic cysts and neuroendocrinemultiple and tumors; endolymphatic sac tumors;bilateralepididymal and broad ligament28%-45%cystadenomas 11 12. SyndromeChromosome Renal Manifestations Other Manifestations Location (Gene)Hereditary papillary 7q31Papillary renal carcinoma Nonerenal carcinomaMET type 1: solid, multiple andtype1(HPRC)bilateralHereditary 1q42-43Papillary renal carcinoma Uterine leiomyomasleiomyomatosis and FH type 2, collecting duct and leiomyosarcomas;renal cell carcinomacarcinoma: solitary,cutaneous leiomyomas(HLRCC) aggressive 12 13. Syndrome Chromosome Renal Manifestations Other ManifestationsLocation (Gene)Birt-Hogg-Dub 17p11.2 Hybrid oncocytic renal tumors, Benign tumors of hairsyndrome (BHD) BHD chromophobe and clear cell follicle (fibrofolliculomas); renal carcinomas, oncocytomas: lung cysts, spontaneous multiple, bilateralpneumothoracesConstitutional 3p; Not known; Clear cell renal carcinoma: Nonechromosome 3 VHL somatic multiple, bilateraltranslocationmutations 84% - 98%13 14. 14 15. Natural History 7% diagnosed incidentally 45% present with localized disease, 25% withlocally advanced disease, 30% with metastaticdisease Lymph node metastases- 9% to 27% (renal hilar,para-aortic and paracaval) Renal vein 21% & IVC 4% Distant metastases- lung (75%), soft tissue (36%),bone (20%), liver (18%), skin (8%) and CNS (8%) 15 16. Clinical Presentation Clinically occult for most of its course. Classic triad (occur in 5%-10% of patients) flank pain, hematuria, palpable abdominal mass Hematuria present 40% of patients Systemic symptoms Anaemia, Fatigue, Cachexia, Wt. Loss, Hypercalcemia, Hepatic Dysfunction Paraneoplastic Syndrome Parathyroid like hormones, erythropoietin, renin, gonadotropins, placental lactogen, prolactin, enteroglucagon, insulin like hormones, adrenocorticotropic hormone and prostaglandins identified in RCC pt. 16 17. Diagnostic Work-Up General-History, Physical examination Laboratory studies CBC, LFTs, alkaline phosphotase, BUN, creatinine, urinalysis Radiographic studies- Increased use of imaging has increased thedetection of renal lesions most of which are simple cysts. X-Ray KUB region Ultrasonography- Excellent in distinguishing cystic from solid masses Intravenous Urography - Starting point for hematuria evaluations and function of contralateral kidney Computed tomography- Provides an excellent assessment of the parenchyma and nodal status. Magnetic Resonance Imaging - excellent demonstration of solid renal masses and is image test of choice to demonstrate extent of vena caval involvement with tumor. Useful in patients with renal insufficiency17 18. Metastatic Work-Up Chest X-ray or Chest CT CT/MRI scan of abdomen or pelvis Bone scan with plan films (for elevated alkaline phosphatase or bone pain). 18 19. Figure : Computed tomography demonstratesa right renal carcinoma (m) with a largecontralateral adrenal metastasis (a).Figure: CT scan shows large left renal masswith calcification (m) invading the left renalvein (arrow). 19 20. Figure: T1-weighted magneticresonance image demonstratestumor (m) and vascular invasion(arrow). Flowing blood (v) in theleft renal vein is black on this scan. Figure A: Axial T1-weighted image demonstrates a large left renal carcinoma with extension into the left renal vein (m) with protrusion into the IVC (v). B: Sagittal T1-weighted image shows the relation of the tumor thrombus (m) to the IVC (v) in the lateral projection.20 21. Robson Modification Of the Flocks & Kadesky Staging of RCCTumor Stage Description IRenal cell carcinoma is confined to the kidneysIIRenal cell carcinoma extends through the renal capsule but isconfined to Gerotas fasciaIII Renal cell carcinoma involves the renal vein or inferior vena cava(IIIA) or the renal hilar lymph nodes (IIIB)IVRenal cell carcinoma has spread to local adjacent organs (otherthan adrenal gland) or to distant sites 21 22. TNM stagingT - primary tumourTX Primary tumour cannot be assessedT0 No evidence of primary tumourT1 Tumour confined to kidney, 4cm but 7cm, confined to kidneyT3 Tumour extends into major veins or adrenal or perinephric tissue but not beyond Gerotas fasciaT3aDirect invasion of adrenal gland, perirenal and/or sinus fatT3bGross extension into renal vein or IVCT3cExtends into IVC above diaphragm or wall of IVCT4 Invasion beyond Gerotas fasciaN - regional lymph nodesNX Nodes cannot be assessedN0 Regional lymph nodes not involvedN1 Metastasis in a single regional lymph nodeN2 Metastases in >1 regional lymph nodeM - distant metastasesMX Metastases cannot be assessedM0 No distant metastasesM1 Distant metastases 22 23. StagingI T1N0M0 IIT2N0M0 T3N0M0- Stage I-III: Localized disease III T1N1M0- Stage IV: Advanced, metastatic T2N1M0diseaseT4N0M0 T4N1M0 IV Any T N2M0 Any T Any N M123 24. Prognostic factors for RCC Pathologic stage5 yr survival T1 - 2 organ confined70-90% T3 50-70% N+, M1 5-30% Tumour size < 4 cm > 90% 4 - 10 cm50% > 10 cm0% Histological type Clear cell 70% Papillary, Chromophobe 85% Multilocular cystic100% Medullary, Collecting duct 0%24 25. Management Localized disease Metastatic disease 25 26. Management of Localized disease Localized disease Surgery Radio Therapy 26 27. Surgery- Radical nephrectomyGold standard treatment for localized RCC withcontralateral normal kidney, adequate surgicalmargin.Principles of Surgery- Early ligation of renal arteryand vein , removal of kidney including Gerotasfascia, removal of ipsilateral adrenal gland, regionallymphadenectomy from crus of diaphragm to aorticbifurcation. 27 28. Nephron Sparing SurgeryIndications 1. Bilateral RCC 2. RCC in a solitary functioning kidney 3. Unilateral RCC with contralateral kidney under threat of its future function (Renal artery stenosis, Chronic pyelonephritis , Hydronephrosis, Ureteral reflux, Calculus disease, Systemic disease such as diabetes ) 4. Tumor less than 4cms with normal opposite kidney. 5. Five year survival rate 75% to 85% 6. Local tumor recurrence of 10% is reported.Other Approaches1. Radio frequency ablations2. Cryo ablation 28 29. Radiotherapy Radiosensitivity of RCC is variable Animal experiments suggest a theoretical benefitto preoperative RT (? Reduce intra-operativeseeding) Historically several series suggested clinicalbenefit to adjuvant (post-op) RT Limited applicability because of long time span,improvements in staging, surgery, changing RTtechnology 29 30. Neo-adjuvant radiotherapy Rotterdam study Radical nephrectomy vs neo-adjuvant RT (30Gy/15#APPA) plus nephrectomy No overall survival or metastasis-free survival advantage(both 50% 5-year survival) No improvement in resectability Further study to 40Gy - still no advantage Swedish study Poorer 5-year survival with pre-op RT (47% vs 63%)!30 31. Adjuvant radiotherapy Some early studies suggested advantage to post-opRT but poorly designed and reported Newcastle (UK) study Poorer survival with adjuvant RT (55Gy) vs surgery alone Not stratified by grade or stage Copenhagen study Stage II/III disease No difference in RCC relapse Significantly more GI complications (44%) in RT group 19% of deaths attributed to RT complications 31 32. Role of RT MSKCC and Kao retrospective series Potential benefit of RT in selected cases where there is ahigh risk of local failure, ie: Pre-op RT in unresectable, locally-advanced tumours(downstaging), including T3a/T3c T3b (vena cava invasion) doesnt necessarily increase risk of localfailure Incomplete resection with positive margins Lymph node involvement RT in these cases may improve local control butprobably not overall survival Clear role in palliation32 33. RT Techniques High energy photons (10 mv or above) from linearaccelerator Conventional External Beam Radiation. Technique- AP/ PA field AP/PA + Oblique field (in large tumor) Portal Upper- T10 T11 Vertebra Lower- transverse process of L3 Medial-2 cm from midline or covering the opposite renal pelvis Lateral- whole flank or tumor For Rt. Sided tumor field reduction after dose of 3600cGy to4ooocGy Safe dose: 5040 cGy in 180 cGy/# over a period of 5-6 weeks Boost of 540 cGy in 3# to small volume Total dose: 5580 cGy 33 34. RT techniques Pre-op RT 40-50Gy to kidney + lymphatics forunresectable lesions may improve resectability 45-50Gy post-op in 1.8 to 2 Gy daily fractionnephrectomy bed and lymph node drainage site 10-15Gy boost (ie. ~60Gy total) to gross residual disease Include scar to reduce chance of scar recurrence Dose limitations (fully fractionated) Liver D30