Diese Präsentation wurde erfolgreich gemeldet.
Wir verwenden Ihre LinkedIn Profilangaben und Informationen zu Ihren Aktivitäten, um Anzeigen zu personalisieren und Ihnen relevantere Inhalte anzuzeigen. Sie können Ihre Anzeigeneinstellungen jederzeit ändern.
MANAGEMENT OF RENALMANAGEMENT OF RENAL
TUMORSTUMORS
By Dr Anil Gupta
Moderator Dr Renu Madan
Classification of renal tumors
● Renal parenchymal tumors
Adult renal tumors
- Benign renal tumors- angiomyolipoma, oncocy...
Renal Pelvis and Ureter
● > 90% urothelial carcinoma
● Accounts for 7% of all kidney tumors and 5% of all urothelial malig...
Renal parenchymal tumors
WHO classification of renal tumors(2016)
RENAL CELL CARCINOMA
Introduction
● Malignant tumors of the kidney and renal pelvis account for nearly 4% of
cancer cases and over 2% of cancer...
Epidemiology
Increases were seen mainly for localized cancers
- heightened clinical surveillance
- improved diagnostic capabilities
Established
Tobacco exposure
- Increases risk by about 50% in men and 20% in
women
Obesity
- Increases 24% for men and 3...
Genetic factors
Clinical Presentation
● Called “the great mimicker” or “the internist’s tumor”
● Many remain asymptomatic until the late d...
● Anemia (21-41%)
● Elevated sedimentation rate (50-60%)
● Reversible hepatic dysfunction (10-
15%)
● Fever (7-17%)
● Amyl...
GradingFuhrman grading
● A simplified, nuclear grading system, based only on size and shape of
nucleoli, will replace pres...
Prognostic factors
● Overall, tumor related factors such as pathologic stage, tumor size, nuclear grade,
and histologic su...
Normogram
Karakiewicz PI et al
Diagnostic evaluation
●
Baseline workup
- LFT, KFT, Creatinine clearance, CBC, ESR, coagulation study, urinalysis ,
Renal ...
● Emits sounds ( 3 to 7 Mhz) and
receives echo
● Strength of the echo determines the
brightness setting for that cell
whit...
Major criteria for a single simple cyst
are:
● the mass is round and sharply
demarcated with smooth walls
● no echoes (ane...
If US equivocal (complex cyst), or
suggestive of malignancy
● solid or complex
● with internal echoes
● and irregular wall...
CT Imaging
● Radiologist's tumor
● Most reliable method for
detecting and staging renal
cancers
● Ideal CT examination for...
- nephrographic (~90 seconds post
injection)---> has the highest
sensitivity and specificity for renal
masses
- excretory ...
CT provides information on
- Function and morphology of the
contralateral kidney
- Primary tumour extension;
- Venous invo...
MRI
● MRI is used to evaluate solid
tumors seen on CT if a patient is
unable to receive IV contrast.
● Vascular invasion, ...
PET Scan
● For patients with high risk of
metastatic RCC
● Good specificity but suboptimal
senstivity
● At present its bes...
● Intravenous pyelography
Pros
- provide valuable information
pertaining to the pyelocalyceal system
- less resources requ...
Renal tumor biopsy● Can be performed under LA, with core needle or fine needle
● At least two good quality cores should be...
● Complications
- bleeding, infection, arteriovenous fistula, needle track seeding,
pneumothorax
Moreover........
- sampli...
STAGING
- Renal hilar
- Caval (paracaval,
precaval, and retrocaval)
-Interaortocaval
- Aortic (paraaortic, preaortic,
retroaortic)
Clinical Staging
Survival by stage
Management of Localized RCC
(Stage I)
Radical nephrectomy
● Earlier gold standard( Robson et al,
1969)
Prototype
En bloc removal of the kidney and its
perirenal...
● Only 7% of patients with RCC tumors larger than 4 cm have micrometastatic
adrenal involvement
● Adrenalectomy only if
- ...
● Open
● Laparoscopic
- Decreased need for postoperative
analgesic drugs(24 mg vs 40 mg
morphine
- Shorter hospital stay(1...
● Advantage over laproscopic
- improved visualization
- more degree of movements
● Limited evidence currently available
fo...
Complications of Radical Nephrectomy
● Intraoperative complication
- injury to any GIT organs or to any major blood vessel...
Nephron sparing surgery(NSS)
● Partial nephrectomy (PN)
● Standard of care
● Surgical removal of a kidney tumor along with...
Indications of NSS
● Imperative
- solitary kidney
- B/L RCC
● Relative
- opposite kidney dysfunctioning
●
Elective(ideal)
...
● With increasing surgical experience, indications of NSS are increasing and
contraindications decreasing
● Now centrally ...
Surveillance after PN
● Robotic RSS- if compared with laparoscopic RSS
- operative time (189 vs 174 minutes)
- positive ma...
Minimal invasive surgery
● Are Nonsurgical Focal Therapy for Renal Tumors
● Alternative to NSS
● They are
- technically le...
● Present day indication:- small renal tumors who are either poor surgical
candidates or at risk for renal insufficiency, ...
●
Use of lower temperatures (<40o
C) for
destroying tumor
● Now argon based cryoprobes are used
based on joule-thompson pr...
Radiofrequency ablation
● Useof radiofrequency energy to heat tissue
to the point of cellular death
Uses electrocautery kn...
Active surveillance
● Elderly and comorbid patients with incidental small renal masses have a
low RCC-specific mortality a...
Surveillance after surgery
Management of Locally Advanced RCC
(Stage II and III, T4 )
Locally advanced renal carcinoma
● Aim of therapy
Complete excision of the tumor, including resection of the involved bowe...
Neoadjuvant Radiotherapy
●
No difference in 5-year OS
●
Neither study, however, used doses considered adequate to steriliz...
Pattern of failure
Local failure
● 2% to 14%
● Increased in the presence of either lymph
node involvement (21% versus 4%,
...
Adjuvant radiation therapy
● Used high dose/# ( 2.5 Gy/# for total dose of 50 Gy)
● Used small bowel in portal
● Small-bow...
Management of metastatic RCC
Prognostic factors
Cytoreductive surgery
RATIONALE
● Bulky tumors might inhibit key components of the immune system critical
for combating ca...
Cytokine therapy
Interleukin-2
● High-dose interleukin- 2 can achieve long-lasting complete(in 5% to 7%) or
partial remiss...
Adverse effects of cytokine therapy
● Flu like symptoms
● Arthralgias
● Myalgias
● Fever and chills
● malaise
In almost al...
Chemotherapy in metastatic setting
● RCC is a prototype of chemorefractory tumor ( limited or modest responses to
traditio...
ERA OF TARGETED THERAPY
How do they act
EGF
PDGF
VEGF
Pericyte
Endothelial cell
Tumor cell
EGF
PDGF
VEGF
EGF
PDGF
VEGF
HIF-1β
VHL
HIF-1α
HIF-1α
HI...
Rational Targets in RCC (cont’d)
EGF
PDGF
VEGF
Pericyte
Endothelial cell
Tumor cell
EGF
PDGF
VEGF
EGF
PDGF
VEGF
HIF-1β
VHL...
Targets and Inhibitors
Multiple tyrosine kinase inhibitors
Targets several signaling pathways simultaneously
●
Sorafenib- PDGFR,VEGF inhibitor
●
...
● Hand foot syndrome- mild to moderate
● Hypertension- frequent, can be serious if not managed properly
● Cardiovascular e...
● Shown favourable response to sunitinib without any significant
toxicity
Monoclonal antibodies
Anti VEGF
● Directly targets VEGF receptors
● Only approved is Bevacizumab
● Given as bevacizumab + ...
mTOR inhibitors
There is dysregulation of mTOR signaling, which can confer higher
susceptibility to inhibitors of mTOR
● E...
Efficacy of targeted therapy
● The vast majority of tumors eventually become refractory to therapy through
a variety of different, as yet poorly unders...
ESMO guidelines for use of Targeted therapy in RCC
ESMO
Non ccRCC
Role of radiotherapy
● WBRT for brain mets
30 Gy/10# 40Gy/20# or 45Gy/15#
LC at 6m 21% 57%
at 12m 7% 35%
OS at 6m 29% 52%
...
● SBRT for extracranial mets
- stereotactic radiation to lung, liver, and adrenal resulted in complete regression in
30% o...
Sarcomas of the kidney
● represent 1% to 2% of all malignant renal tumors in adults
● peak incidence in the fifth decade o...
WILM'S TUMOR
Wilm's tumor
● Accounts for 6% of all pediatric tumors
● The median age of presentation is 3.5 years
● Presents as abdomin...
● Surgical resection is the primary therapy for this tumor in the United
States- National Wilms Tumor Study Group (NWTS)
●...
Localised unilateral tumour
Preoperative chemotherapy
Two drugs (VCR, ActD) x 4 weeks:
Vincristine: 1.5 mg/m2 intravenous bolus (max 2mg) weeks 1, 2, ...
Histology
● Favourable histology
- 9 out of 10 wilm's tumor
- Good prognosis
● Unfavourable histology
- Anaplasia, heterol...
Risk stratification
Staging
● By children's oncology group(COG)
● It is Post operative staging
Stage I - Cancer is limited to the kidney and c...
Postoperative chemotherapy
STAGE I, LOW RISK
- NO ADJUVANT TREATMENT
Metastatic Tumors
Drugs (VCR, Act D, Doxorubicin) x 6 weeks
Vincristine; 1.5 mg/m2 intravenous bolus (max 2mg)
Actinomycin D: 45 microgram/K...
Postoperative chemotherapy
Stage V- B/L renal tumors
PREOPERATIVE CHEMOTHERAPY
● If localized B/L renal tumor- chemotherapy similar to localized WT
● If metastatic B/L tumor- ...
Drug toxicity
● Hematological toxicity- myelosuppresive chemotherapy.
Mx defer chemotherapy if ANC< 1000, platelets< 1 lac...
● Secondary infections- herpes relapse due to relative
immunocompromised state.
Mx aciclovir, restart chemo 1 week after r...
Aim of radiotherapy
1.To prevent abdominal relapse.
2.To increase control of pulmonary metastases in patients not achievin...
Timing of radiotherapy
● RT to be started on day 9 and no longer than 14 days
● Delay results in abdominal tumor recurrenc...
COG renal tumor protocol for radiation therapy
Flank irradiation
● INDICATIONS
- intermediate risk, stage III
- high risk stage II and III – except stage II
blastemal ty...
Whole abdomen irradiation
● If peritoneal tumor spillage
● AP-PA, 6 MV
● Upper margin- includes diaphragm
● Lower margin- ...
Whole lung irradiation
● For pulmonary mets
● A lateral radiograph of the chest
taken ascertain treatment volume
● Dose 15...
● Hepatic RT
- for liver mets
- whole liver RT can be given if diffuse
mets
- preferred is focal RT
-20 Gy may be given to...
Radiation Toxicity
Late effects
● Scoliosis
● Congestive heart failure
● Pregnancy related adverse
effects
● Secondary mal...
Relapse
● The prognosis of children with relapsed WT depends on tumor histology,
initial stage, site of relapse, previous ...
CONCLUSION
● Renal tumors are uncommon
● RCC is mc malignancy
● Radioresistant and chemoresistant
➢ Localized - Partial ne...
THANK YOU
Management of renal cell carcinoma and wilms' tumor
Management of renal cell carcinoma and wilms' tumor
Management of renal cell carcinoma and wilms' tumor
Management of renal cell carcinoma and wilms' tumor
Management of renal cell carcinoma and wilms' tumor
Management of renal cell carcinoma and wilms' tumor
Nächste SlideShare
Wird geladen in …5
×

Management of renal cell carcinoma and wilms' tumor

management of renal cell carcinoma and wilm's tumor

  • Loggen Sie sich ein, um Kommentare anzuzeigen.

Management of renal cell carcinoma and wilms' tumor

  1. 1. MANAGEMENT OF RENALMANAGEMENT OF RENAL TUMORSTUMORS By Dr Anil Gupta Moderator Dr Renu Madan
  2. 2. Classification of renal tumors ● Renal parenchymal tumors Adult renal tumors - Benign renal tumors- angiomyolipoma, oncocytoma, adenoma, cysts - Malignant renal tumors- Renal cell carcinoma(mc), sarcoma, lymphoma Paediatric renal tumors- wilm's tumor, rhabdoid tumor ● Renal Pelvis and Ureter- urothelial carcinoma
  3. 3. Renal Pelvis and Ureter ● > 90% urothelial carcinoma ● Accounts for 7% of all kidney tumors and 5% of all urothelial malignancies ● Staging similar to bladder cancer ● Treated in the line of bladder cancer
  4. 4. Renal parenchymal tumors
  5. 5. WHO classification of renal tumors(2016)
  6. 6. RENAL CELL CARCINOMA
  7. 7. Introduction ● Malignant tumors of the kidney and renal pelvis account for nearly 4% of cancer cases and over 2% of cancer deaths in the United States ● RCC represents over 90% of all malignancies of the kidney in adults ● Male:Female ratio is 2:1 ● It predominantly in the sixth to eighth decade of life with median age at diagnosis around 64 years of age ● Highly vascular ● Not grossly infiltrative, except some collecting duct RCC and some sarcomatoid variants ● No reliable histologic or ultrastructural criteria to differentiate benign from malignant renal cell epithelial tumors, except oncocytoma which is always benign
  8. 8. Epidemiology
  9. 9. Increases were seen mainly for localized cancers - heightened clinical surveillance - improved diagnostic capabilities
  10. 10. Established Tobacco exposure - Increases risk by about 50% in men and 20% in women Obesity - Increases 24% for men and 34% for women for every 5 kg/m2 increase in BMI Hypertension Genetic factors - Von Hippel-Lindau (VHL) syndrome - heriditary papillary RCC - heriditary leiomyoma RCC - Birt-Hogg-Dube syndrome(BHD) - TS -ADPKD Risk Factors Putative (generally considered to be) Lead compounds Various chemicals (e.g., aromatic hydrocarbons) Trichloroethylene exposure Occupational exposure (metal, chemical, rubber, and printing industries) Asbestos or cadmium exposure CRF on dialysis  and antihypertensive Radiation therapy Dietary (high fat/protein and low fruits/vegetables)
  11. 11. Genetic factors
  12. 12. Clinical Presentation ● Called “the great mimicker” or “the internist’s tumor” ● Many remain asymptomatic until the late disease stages ● Classic triad - unilateral flank pain, hematuria, and palpable mass in 6-10% ● Propensity to present with manifold clinical signs, symptoms, and paraneoplastic syndromes on the basis of local tumor extent, distant spread, biological activity ● Can be true incidental tumors, classic triad symptoms, and constitutional symptoms (weight loss, fever, night sweats, anorexia, cough, malaise, etc.)
  13. 13. ● Anemia (21-41%) ● Elevated sedimentation rate (50-60%) ● Reversible hepatic dysfunction (10- 15%) ● Fever (7-17%) ● Amyloidosis (3-5%) ● Neuromyopathy (3%) ● Hypercalcemia (3-6%) Paraneoplastic syndromes ● Erythrocytosis (3-4%) ● Hypertension (22-38%) ● Elevated human chorionic gonadotropin levels ● Cushing syndrome ● Hyperprolactinemia ● Ectopic insulin and glucagon production ● Raised alkaline phosphatase levels (10%) ● Cachexia, weight loss (35%Stauffer syndrome - liver dysfunction secondary to RCC - due to production of hepatotoxins or IL-6, IL-8
  14. 14. GradingFuhrman grading ● A simplified, nuclear grading system, based only on size and shape of nucleoli, will replace present system (ISUP conference 2015)
  15. 15. Prognostic factors ● Overall, tumor related factors such as pathologic stage, tumor size, nuclear grade, and histologic subtype= independent ● Patient related factors such as CKD and co-morbidity have a significant impact on overall survival ● Clinical findings s/o compromised prognosis in presumed localized RCC - Symptomatic presentation - Weight loss of more than 10% of body weight - Poor performance status ● Other – molecular prognostic factors,
  16. 16. Normogram Karakiewicz PI et al
  17. 17. Diagnostic evaluation ● Baseline workup - LFT, KFT, Creatinine clearance, CBC, ESR, coagulation study, urinalysis , Renal scintigraphy ● Essential workup CT Scan ● Complimentary workup Ultrasound, MRI, PET, renal tumor biopsy
  18. 18. ● Emits sounds ( 3 to 7 Mhz) and receives echo ● Strength of the echo determines the brightness setting for that cell white for a strong echo, black for a weak echo, and varying shades of grey for everything in between . Ultrasonography Normal Kidney ● Measures 9-11 cm's ● Has the same extent of echoes as liver ● Cortex measures about 2.5 cm's ● Central echoes are from fat surrounding renal pelvis. ● Renal pelvis is filled with urine and is echo free. Note the posterior enhancement behind renal pelvis
  19. 19. Major criteria for a single simple cyst are: ● the mass is round and sharply demarcated with smooth walls ● no echoes (anechoic) within mass ● strong posterior wall echo indicating good sound transmission through the cyst
  20. 20. If US equivocal (complex cyst), or suggestive of malignancy ● solid or complex ● with internal echoes ● and irregular walls ● if calcifications or septae are seen ● if multiple cysts are clustered so that they may be masking underlying carcinoma PROCEED TO CT....
  21. 21. CT Imaging ● Radiologist's tumor ● Most reliable method for detecting and staging renal cancers ● Ideal CT examination for renal masses ● - precontrast ● - arterial phase (~25 seconds post injection)---> useful for identifying the renal arteries and for hypervascular masses
  22. 22. - nephrographic (~90 seconds post injection)---> has the highest sensitivity and specificity for renal masses - excretory phase (~5–7 minutes post injection---> assessment of collecting system and renal pelvic involvement by a tumo ● A change of 15 or more HUs demonstrates enhancement
  23. 23. CT provides information on - Function and morphology of the contralateral kidney - Primary tumour extension; - Venous involvement; - Enlargement of locoregional LNs; - Condition of the adrenal glands and other solid organs ● A typical finding of RCC - heterogeneous pattern of enhancement -enhancement of iv contrast material by more than 15 HU should be considered an RCC until proved otherwise
  24. 24. MRI ● MRI is used to evaluate solid tumors seen on CT if a patient is unable to receive IV contrast. ● Vascular invasion, IVC thrombi are better demonstrated than CT ● Using bight blood technique running blood shows bright signals except thrombus which shows as defects within the lumen
  25. 25. PET Scan ● For patients with high risk of metastatic RCC ● Good specificity but suboptimal senstivity ● At present its best role is for patients with equivocal findings in conventional imaging ● Radiolabelled monoclonal antibody to CA-IX is virtually present in all ccRCC ● Monoclonal antibody G250 labelled PET is explored
  26. 26. ● Intravenous pyelography Pros - provide valuable information pertaining to the pyelocalyceal system - less resources required Cons - limited sensitivity for renal parenchymal pathologies and small renal masses - time consuming -Contrast toxicity Renal angiogram - now limited role - guiding the operative approach when attempting to perform a partial nephrectomy
  27. 27. Renal tumor biopsy● Can be performed under LA, with core needle or fine needle ● At least two good quality cores should be obtained ● Peripheral biopsies are preferable for larger tumours, to avoid areas of central necrosis ● A coaxial technique allows multiple biopsies ● Sensitivity- 99.1 % ● Specificity – 99.7% ● Diagnosis of tumour histotype is good
  28. 28. ● Complications - bleeding, infection, arteriovenous fistula, needle track seeding, pneumothorax Moreover........ - sampling error, -difficulty interpreting limited tissue - now we have improved diagnostic accuracy of imaging modalities 90% of solid renal masses thought to be suspicious for RCC on imaging prove to be RCC on final pathologic analysis ● Present day indications - radiologically indeterminate renal masses - select patient kept on active surveillance with small renal mass - obtain histology before ablative treatments - select the most suitable form of medical and surgical treatment strategy in the setting of metastatic disease
  29. 29. STAGING
  30. 30. - Renal hilar - Caval (paracaval, precaval, and retrocaval) -Interaortocaval - Aortic (paraaortic, preaortic, retroaortic)
  31. 31. Clinical Staging
  32. 32. Survival by stage
  33. 33. Management of Localized RCC (Stage I)
  34. 34. Radical nephrectomy ● Earlier gold standard( Robson et al, 1969) Prototype En bloc removal of the kidney and its perirenal fat, enveloping Gerota's fascia with I/L adrenal, proximal one- half of the ureter, and lymph nodes dissection from crus till the area of transection of the renal vessels( or aortic bifurcation) ● Much has changed now
  35. 35. ● Only 7% of patients with RCC tumors larger than 4 cm have micrometastatic adrenal involvement ● Adrenalectomy only if - extensive renal involvement - locally advanced - upper pole tumor - SRM adjacent to adrenals ● LN dissection still contoversial ● Recent studies failed to show survival benefit ● More accurate pathological staging present day indications of LN dissection - high grade tumor - sarcomatoid component - histologic tumor necrosis - large size of tumor (>10cm) - pT3 or pT4 Changes in radical nephrectomy
  36. 36. ● Open ● Laparoscopic - Decreased need for postoperative analgesic drugs(24 mg vs 40 mg morphine - Shorter hospital stay(1.5 day vs 5 day - Shorter recovery period (4 wk vs 8 wk) Laparoscopy have similar DFS at 5 years and 10 years.as open surgery Limitations of Laparoscopic procedure -two-dimensional imaging -restricted range of motion of the instruments -poor ergonomic positioning of the surgeon
  37. 37. ● Advantage over laproscopic - improved visualization - more degree of movements ● Limited evidence currently available for radical nephrectomy Robot assisted Radical nephrectomy
  38. 38. Complications of Radical Nephrectomy ● Intraoperative complication - injury to any GIT organs or to any major blood vessels, pleural injuries can result in pneumothorax. ● Postop complications- secondary hemorrhage, atelectasis, ileus, superficial and deep wound infections,renal failure, and incisional hernia. ● Other well-recognized systemic complications include MI, CHF, pulmonary embolism, CVA, pneumonia, and thrombophlebitis ● Results in CKD
  39. 39. Nephron sparing surgery(NSS) ● Partial nephrectomy (PN) ● Standard of care ● Surgical removal of a kidney tumor along with a thin rim of normal kidney ● Preserves renal functioning
  40. 40. Indications of NSS ● Imperative - solitary kidney - B/L RCC ● Relative - opposite kidney dysfunctioning ● Elective(ideal) - easily resectable, small (<4 cm), solitary, exophytic renal tumor, not a candidate for surveillance, and whose medical condition is good enough to undergo surgery and to benefit from it
  41. 41. ● With increasing surgical experience, indications of NSS are increasing and contraindications decreasing ● Now centrally located tumors can also be resected by NSS ● can also be effectively and safely used to treat patients with tumors up to 7 cm in diameter ● improved preservation of renal function, superior cardiac outcomes, and improved overall survival, avoids overtreatment og indolent benign tumors ● Clinical stage1 renal massesrecommendsnephron-sparing surgery as standard of care(AUA) - mean warm ischemia time (27.8 vs 17.5 minutes) - major intraoperative complications (5% vs 0%) - postoperative complications(11% vs 2%) Laparoscopic RSSLaparoscopic RSS - operative time (3 vs 3.9 hrs) - blood loss (125 vs 250 ml) - average recovery time was 4 vs 6 weeks - analgesic requirement (20.2 vs 252.5 mg morphine) - hospital stay ( 2 vs 5 d)
  42. 42. Surveillance after PN ● Robotic RSS- if compared with laparoscopic RSS - operative time (189 vs 174 minutes) - positive margin rate (3.9% vs 1%) - Intraoperative blood loss (155 vs 196 ml) - length of hospital stay (2.4 vs 2.7 days) - Warm ischemia time(19.7 vs 28.4 minutes) -Postoperative complication (8.6% vs 10.2%).
  43. 43. Minimal invasive surgery ● Are Nonsurgical Focal Therapy for Renal Tumors ● Alternative to NSS ● They are - technically less demanding - shorter recovery and fewer complications than extirpative surgery - minimal impact on postablation renal function - can be deployed in open,laparoscopic, or percutaneous procedures
  44. 44. ● Present day indication:- small renal tumors who are either poor surgical candidates or at risk for renal insufficiency, including patients with solitary kidneys, bilateral renal tumors, hereditary syndromes such as von Hippel- Landau disease, and renal insufficiency ● Cryoablation ● Radiofrequency ablation ● Microwave ablation ● Laser ablation ● High-intensity focused US ablation ● SBRT- as an alternative to thermal ablation is in its infancy
  45. 45. ● Use of lower temperatures (<40o C) for destroying tumor ● Now argon based cryoprobes are used based on joule-thompson principle ● Tissue destruction occurs due to both freezing and thawing processes MOA formation of ice crystals within cells coagulation of blood interrupting bloodflow causing ischemia and cell death induction of apoptosis, the so- called programmed cell death cascade ● the current recommendation is to perform a double freeze-thaw cycle to ensure complete cellular death Cryoablation
  46. 46. Radiofrequency ablation ● Useof radiofrequency energy to heat tissue to the point of cellular death Uses electrocautery knife alternating electric current delivered to target tissue vibration of ions within tissue and resulting in molecular friction and heat production cellular protein denaturation and cell membranedisintegration
  47. 47. Active surveillance ● Elderly and comorbid patients with incidental small renal masses have a low RCC-specific mortality and significant competing-cause mortality ● These patients can be kept for active surveillance
  48. 48. Surveillance after surgery
  49. 49. Management of Locally Advanced RCC (Stage II and III, T4 )
  50. 50. Locally advanced renal carcinoma ● Aim of therapy Complete excision of the tumor, including resection of the involved bowel, spleen, or abdominal wall muscles ● Radical nephrectomy is standard of care ● Extended operations with en bloc resection of adjacent organs are occasionally indicated. ● IVC thrombus is curable and thombectomy should be done ● 90% died of disease at a median of 12 months after surgery ● Extensive lymphadenectomy in RN remains controversial, as a randomized trial failed to show a distinct advantage ● R0 resection margins only in 63%
  51. 51. Neoadjuvant Radiotherapy ● No difference in 5-year OS ● Neither study, however, used doses considered adequate to sterilize even microscopic disease by current standards. ● Patients were eligible for participation, regardless of the stage of their lesions. ● Two prospective randomized studies failed to show benefit of preoperative RT
  52. 52. Pattern of failure Local failure ● 2% to 14% ● Increased in the presence of either lymph node involvement (21% versus 4%, Distant metastasis ● 26% in 7 yrs ● No survival benefit or DFS seen with systemic chemotherapy or targeted therapy
  53. 53. Adjuvant radiation therapy ● Used high dose/# ( 2.5 Gy/# for total dose of 50 Gy) ● Used small bowel in portal ● Small-bowel toxicity ● Hepatic dysfunction ● No survival benefit ● Need a multi-institutional study with hundreds of patients who are treated with meticulous treatment planning and a well-thought-out fractionation scheme for definite conclusion ● Use of IMRT ca reduce toxicity
  54. 54. Management of metastatic RCC
  55. 55. Prognostic factors
  56. 56. Cytoreductive surgery RATIONALE ● Bulky tumors might inhibit key components of the immune system critical for combating cancer-- spontaneous regression of metastatic lesions ● Bulky tumor reduces response of systemic therapy ● Removal of large primary tumors may provide symptomatic benefit ● Surgery alone less likely to alter outcome Dekernion et al, 1978 ● Several studies favoured nephrectomy f/b adjuvant therapy Metastectomy ● Solitary metastaic lesion have 5 yr survival rate of 24%( 4% in multiple metastasis) ● Resection along with nephrectomy is a/w 13% to 50% 5yr survival Piltz et al
  57. 57. Cytokine therapy Interleukin-2 ● High-dose interleukin- 2 can achieve long-lasting complete(in 5% to 7%) or partial remissions in a small subset of patients with predominantly clear cell carcinoma ● Lower-dose IL-2 is non inferior Interferon- α ● The response rates to interferon observed in the two study arms, OS was improved in the surgery-plus interferon arm (median 11.1 vs. 8.1 months for interferon alone,P = .05) Flanigan RC et al
  58. 58. Adverse effects of cytokine therapy ● Flu like symptoms ● Arthralgias ● Myalgias ● Fever and chills ● malaise In almost all patients after adminstration ● Adverse effects Expensive ● Not very good response ● Availability of targeted therapy NOT USED NOW
  59. 59. Chemotherapy in metastatic setting ● RCC is a prototype of chemorefractory tumor ( limited or modest responses to traditional chemotherpaeutics) ● Expression of multi drug resistance (MDR) proteins - Eg: MDR-1(also known as p-glycoproteins) and MDR related proteins - Act as energy dependent efflux pumps for variety of hydrophobic compounds - contibute to chemorefractory nature of advanced RCC ● However there are some extra features - RCC is also resistant to drugs like cisplatin and others( that are not handled by MDR proteins) - downregulation of MDR-1 in high grade tumors and metastatic RCC ● Medroxyprogestrone acetate was Ist systemic agent used for metastatic RCC ● Low response rates, but some tumor regression and symptom reduction seen ● Only 5-FU + Gemcitabine has shown 10-20% response in some variety
  60. 60. ERA OF TARGETED THERAPY
  61. 61. How do they act EGF PDGF VEGF Pericyte Endothelial cell Tumor cell EGF PDGF VEGF EGF PDGF VEGF HIF-1β VHL HIF-1α HIF-1α HIF-1α RAS RAF MEK ERK RAS RAF MEK ERK RAS RAF MEK ERK Paracrine Function Paracrine Function Autocrine Function
  62. 62. Rational Targets in RCC (cont’d) EGF PDGF VEGF Pericyte Endothelial cell Tumor cell EGF PDGF VEGF EGF PDGF VEGF HIF-1β VHL HIF-1α HIF-1α HIF-1α RAS RAF MEK ERK RAS RAF MEK ERK RAS RAF MEK ERK Bevacizumab Bevacizumab Bevacizumab Sunitinib Sunitinib Sunitinib Sunitinib Sorafenib Sorafenib Sorafenib Sorafenib Sorafenib Sorafenib Sorafenib
  63. 63. Targets and Inhibitors
  64. 64. Multiple tyrosine kinase inhibitors Targets several signaling pathways simultaneously ● Sorafenib- PDGFR,VEGF inhibitor ● Sunitinib- PDGFR,VEGF, stem cell factor receptor (KIT) inhibitor ● Pazopinib ● Axitinib ● Cabozatinib ● Lenvatinib ● Tivozinib ● Regorafenib- inhibits both VEGFR-2 and TIE2 TK ● Dovitinib- has activity against VEGF-R1/2/3, PDGF-R, c-kit, FLT3 and additionally fibroblast growth factor (FGF) receptor 1, 2 and 3
  65. 65. ● Hand foot syndrome- mild to moderate ● Hypertension- frequent, can be serious if not managed properly ● Cardiovascular events ● Haemorrhage- can be life threatening ● Hepatotoxicity- in 3% cases on pazopinib Adverse effects
  66. 66. ● Shown favourable response to sunitinib without any significant toxicity
  67. 67. Monoclonal antibodies Anti VEGF ● Directly targets VEGF receptors ● Only approved is Bevacizumab ● Given as bevacizumab + Interferon- α IgG4 anti-PD-1 ● Nivolumab ● Blocks a negative regulator of T-cell activation and response, thus allowing the immune system to attack the tumor ● 2nd line treatment for renal cell carcinoma
  68. 68. mTOR inhibitors There is dysregulation of mTOR signaling, which can confer higher susceptibility to inhibitors of mTOR ● Everolimus ● Temsirolimus ● Has immunosupressive action- can cause infections ● Hypercholestrolemia and hyperglycemia
  69. 69. Efficacy of targeted therapy
  70. 70. ● The vast majority of tumors eventually become refractory to therapy through a variety of different, as yet poorly understood, mechanisms after a median time 0f 5-11 months ● Novel agents and rational combinations are in development for the treatment of mRCC in an attempt to address these resistance mechanisms, and reduce severe side effects. Problem with targeted therapy
  71. 71. ESMO guidelines for use of Targeted therapy in RCC ESMO
  72. 72. Non ccRCC
  73. 73. Role of radiotherapy ● WBRT for brain mets 30 Gy/10# 40Gy/20# or 45Gy/15# LC at 6m 21% 57% at 12m 7% 35% OS at 6m 29% 52% at 12m 13% 47% –->dose escalation beyong 30Gy has favourable outcome Shuto T, et al. ● SRS for focal brain lesion > 3cm- resection >2cm with symptomatic peritumoral edema- resection >2 asymptomatic- gamma knife sx <2 cm – gamma knife sx J.P Kavolius et al
  74. 74. ● SBRT for extracranial mets - stereotactic radiation to lung, liver, and adrenal resulted in complete regression in 30% of cases and either partial regression or stabilization of the lesions in 60% ● Conventional RT for extracranial metastases - Palliative radiotherapy is effective in relieving symptoms from metastatic RCC. - solitary bone metastasis- long term survival - Post metastectomy RT to prevent recurrence - Complete resolution painful RCC cutaneous metastasis 37.5 Gy/13# electron case report
  75. 75. Sarcomas of the kidney ● represent 1% to 2% of all malignant renal tumors in adults ● peak incidence in the fifth decade of life ● more lethal than sarcoma of any other genitourinary site ● Suspected if - growth to large size in the absence of lymphadenopathy - presence of fat or bone suggestive of liposarcoma or osteosarcoma, - hypovascular pattern on angiography ● Managed by surgical resection ± chemotherapy ± RT
  76. 76. WILM'S TUMOR
  77. 77. Wilm's tumor ● Accounts for 6% of all pediatric tumors ● The median age of presentation is 3.5 years ● Presents as abdominal mass,abdominal pain or incidental ● WT1 (11p13), WT2 (11p15), and genes in the WNT signaling pathway are implicated in the development of Wilms’ tumor. ● Also a/w WAGR, the Beckwith- Wiedemann syndrome, and the Denys- Drash syndrome ● MR scanning is the recommended gold standard for abdominal imaging.
  78. 78. ● Surgical resection is the primary therapy for this tumor in the United States- National Wilms Tumor Study Group (NWTS) ● Preoperative chemotherapy is routinely used in Europe- International Society of Pediatric Oncology (SIOP) ● PGI follows SIOP guidelines 2001, ammended in 2004 ● Has allowed reduction of treatment intensity ● 1.5 % benign tumors asre treated as wilms ● No difference in 5 yr EFS
  79. 79. Localised unilateral tumour
  80. 80. Preoperative chemotherapy Two drugs (VCR, ActD) x 4 weeks: Vincristine: 1.5 mg/m2 intravenous bolus (max 2mg) weeks 1, 2, 3, 4 (5th dose can be given if week 5 falls before planned surgery) Actinomycin D: 45 microgram/Kg intravenous bolus (max 2mg), weeks 1, 3 Give 66% of above doses for children weighing <12 Kg. If age < 6mths dose reduce to 50% of each drug. Reassessment imaging at week 4 Surgery should be planned for week 5-6
  81. 81. Histology ● Favourable histology - 9 out of 10 wilm's tumor - Good prognosis ● Unfavourable histology - Anaplasia, heterologous epithelial or stromal components , including mucinous or squamous epithelium,skeletal muscle, cartilage, osteoid, or fat ● Anaplastic wilm's tumor
  82. 82. Risk stratification
  83. 83. Staging ● By children's oncology group(COG) ● It is Post operative staging Stage I - Cancer is limited to the kidney and can be completely removed by surgery Stage II - Cancer has spread to the areas surrounding the kidney and can be completely removed by surgery Stage III - Cancer has spread to the areas surrounding the kidney, including blood vessels, lymph nodes, or other nearby organs, and cannot be completely removed by surgery, Node +ve, residual disease after surgery, tumour rupture Stage IV - Cancer has spread into organs such as the lungs, liver, bone, and brain Stage V - Tumors are found in both kidneys. Each kidney is staged separately
  84. 84. Postoperative chemotherapy STAGE I, LOW RISK - NO ADJUVANT TREATMENT
  85. 85. Metastatic Tumors
  86. 86. Drugs (VCR, Act D, Doxorubicin) x 6 weeks Vincristine; 1.5 mg/m2 intravenous bolus (max 2mg) Actinomycin D: 45 microgram/Kg intravenous bolus (max 2mg) Doxorubicin 50 mg/m2 intravenous infusion over 4-6 hours weeks Give 66% of above doses for children weighing <12 Kg. If age <6 mths dose reduce to 50% of each drug Reassessment imaging (3D) at week 6 Surgery should be planned for week 7-8 Preoperative chemotherapy
  87. 87. Postoperative chemotherapy
  88. 88. Stage V- B/L renal tumors
  89. 89. PREOPERATIVE CHEMOTHERAPY ● If localized B/L renal tumor- chemotherapy similar to localized WT ● If metastatic B/L tumor- chemotherapy similar to metastatic WT ● Continue till it shows signs of tumor regression, but not beyond 12weeks ● If nephron sparing surgery not feasible then, carboplatin-etoposide chemo may enable tumor regression NEPHRON SPARING SURGERY POSTOPERATIVE CHEMOTHERAPY ● Chemotherapy directed highest stage lesion kidney
  90. 90. Drug toxicity ● Hematological toxicity- myelosuppresive chemotherapy. Mx defer chemotherapy if ANC< 1000, platelets< 1 lac, Hb< 7g ● GI toxicity- emetogenic drugs, VCR causes constipation. Mx- antiemetics, laxatives, rehydration ● Hepatic complications – actinomycin D Mx- monitoring with LFT ● Cardiac complications- with doxorubicin Mx- prolonged infusion, monitioring with ECHO, cumulative dose <200mg/m2
  91. 91. ● Secondary infections- herpes relapse due to relative immunocompromised state. Mx aciclovir, restart chemo 1 week after resolution of rash ● Neurological toxicity- muscle weakness, hyporeflexia caused by vincristine Mx in case of severe neuritis skip the dose of VCR ● Bladder and renal toxicity- cyclophosphamide can cause hemorrhagic cystitis Mx prophylactic use of MESNA, I.V fluids and diuretics
  92. 92. Aim of radiotherapy 1.To prevent abdominal relapse. 2.To increase control of pulmonary metastases in patients not achieving complete remission following chemotherapy and surgery 3.To increase control of hepatic metastases in patients who do not achieve complete remission following chemotherapy and surgery 4.To increase control of brain and bone metastases
  93. 93. Timing of radiotherapy ● RT to be started on day 9 and no longer than 14 days ● Delay results in abdominal tumor recurrence ( NWTS-3 and NWTS-4) ● This is often not feasible and so RT should commence as soon as is practicable ● If both pumonary and abdominal RT indicated, better to give both together to prevent overlap toxicity
  94. 94. COG renal tumor protocol for radiation therapy
  95. 95. Flank irradiation ● INDICATIONS - intermediate risk, stage III - high risk stage II and III – except stage II blastemal type - Stage IV and V disease treated according to local stage TECHNIQUE - AP-PA, 6 MV photons field is preferred - PTV- post op bed with 1 cm margin - Medial border must cross midline to prevent growth disturbances Whole abdominal irradiation..
  96. 96. Whole abdomen irradiation ● If peritoneal tumor spillage ● AP-PA, 6 MV ● Upper margin- includes diaphragm ● Lower margin- lower border of obturator foramen with shielding of acetabulum and femoral head ● Lateral margin- flashing in air
  97. 97. Whole lung irradiation ● For pulmonary mets ● A lateral radiograph of the chest taken ascertain treatment volume ● Dose 15 Gy/ 10# ● A boost of 5-10 Gy could be considered for areas of gross residual disease
  98. 98. ● Hepatic RT - for liver mets - whole liver RT can be given if diffuse mets - preferred is focal RT -20 Gy may be given to the area of R1 resection of metastases(2 Gy/#) ● Whole brain RT - for brain mets - 25.5 Gy to whole brain f/b boost of 4.5 Gy with 1.5 Gy/#
  99. 99. Radiation Toxicity Late effects ● Scoliosis ● Congestive heart failure ● Pregnancy related adverse effects ● Secondary malignancy ● End stage renal disease Acute effects ● Myelotoxicity - stop if neutrophil <500, resume if >1000 - stop if platelet count <25,000, resume if >50,000 - minimum Hb should be 10.0 g, transfusion to be done if less ● GI toxicity- nausea, vomiting, diarrhea
  100. 100. Relapse ● The prognosis of children with relapsed WT depends on tumor histology, initial stage, site of relapse, previous therapy, and time from initial diagnosis to relapse ● The 3-year postrelapse survival rates were 44%, 28%, and 11% when the relapse was confined to the lungs, abdomen, or other sites respectively ● The salvage regiment consisted of surgery when feasible, RT, and alternating courses of vincristine, doxorubicin, cyclophosphamide, and etoposide/cyclophosphamide
  101. 101. CONCLUSION ● Renal tumors are uncommon ● RCC is mc malignancy ● Radioresistant and chemoresistant ➢ Localized - Partial nephrectomy ➢ Locally advanced- Radical nephrectomy- no effective adjuvant therapy available ➢ Metastatic - Cytoreductive nephrectomy f/b targeted therapy ± RT ● Earlier detection has improved cure rate ● Many newer targeted therapy are underdevelopment which may improve survival rate ● Wilm's tumor is most common paediatric renal tumor ● Very chemosensitive and radiosensitive ● Multi modality approach has improved survival rate drastically
  102. 102. THANK YOU

×