Neuroblastoma & Wilms tumor.pptx

presentation on Neuroblastoma & Wilms tumor

1. Neuroblastoma & Wilms tumor By Dr Irfan Malik PGR URO IKD

2. Learning objectives Background Incidence Embryology Genetics Pathophysiology Clinical presentation Diagnosis Management Prognosis Follow up

3. Neublastoma Background Neuroblastoma is the most common extracranial solid tumor of childhood . Neuroblastoma is known to arise from cells of the neural crest that form the adrenal medulla and sympathetic ganglia. Tumors may occur anywhere along the sympathetic chain within the neck, thorax, retroperitoneum , or pelvis or in the adrenal gland.

4. Continue These tumors can undergo spontaneous regression , differentiate to benign neoplasms, or exhibit extremely malignant behavior . Unpredictable behaviour Retroperitoneum 75% Adrenal 50% paravertebral ganglia 25%

5. Incidence 8% to 10% of all childhood cancers. Annual incidence is 10 cases per million in US. Most common tumor of infancy. Median age at diagnosis is 18 months which reduces to 9 months in familial form.

6. Embryology Neuroblastoma is known to arise from cells of the neural crest that form the adrenal medulla and sympathetic ganglia.

7. Genetics 40% in advance disease 5 t0 6% in low stage disease Adverse prognostic indicator MYCN oncogene at 2p24 25 to 35% cases Adverse prognosis IT ARISES DUE TO SOMATIC MUTATION IN THE BODY CELLS

8. Prognostic Markers Intensity of chemotherapy is determined not only by staging of tumor but also by its biologic markers . Favourable markers unfavourable markers DNA Aneuploidy > > Amplification of the MYCN oncogene at 2p24 > >Deletion of the short arm of chromosome 1p, > > 11q deletion , > > 17q gain

9. Pathophysiology Neuroblastoma Malignant Ganglioneuroblastoma Intermediate Ganglioneuroma Benign Unpredictable tumor Natural Course?

10. Shimada classification Stroma Rich Stroma Poor Nodular Intermixed Favourable Unfavourable well differentiated Based on the patient's age at diagnosis , the degree of histologic maturation, and the mitotic rate.

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13. Clinical Presentation Local disease abdominal pain or a palpable mass Metastatic bone or joint pain, periorbital ecchymosis. Thoracic lesions may produce respiratory symptoms of cough or dyspnea . Neurologic deficits as a result of cord compression. Extrinsic compression of the bowel and bladder can produce symptoms of urinary retention and constipation Metastases are present in 70% of patients with neuroblastoma at diagnosis.

14. Para neoplastic syndrom e . Catecholamine mimic pheochromocytoma VIP severe watery diarrhea and hypokalemia . Unusual presentation. acute myoclonic encephalopathy, in which patients develop myoclonus, rapid multidirectional eye movements ( opsoclonus ), and ataxia. It is thought to result from an interaction of antibodies produced against the neuroblastoma to normal neural tissues.

15. Diagnosis Laboratory Evaluation urinary metabolites of catecholamines , vanillylmandelic acid (VMA) and homovanillic acid (HVA), are found in 90% to 95% of patients. Anemia . In children with widespread bone marrow involvement.

16. Imaging Plain radiographs. May demonstrate a calcified abdominal or posterior mediastinal mass . CT. local extent of the primary tumors and vascular involvement. Invasion of the renal parenchyma is not common, but it can be detected radiographically by CT. The finding of intratumoral calcifications , vascular encasement, or both on preoperative CT may help distinguish neuroblastoma from Wilms tumor .

17. Metaiodobenzylguanidine (MIBG ) scan. Use 123I-MIBG determine the extent of disease and detect tumor recurrence after completion of therapy. Positron emission tomography (PET ) can be used if MIBG can not be used or not available.

18. MRI . local extent & vascular involvement. MRI has advantages over CT in the evaluation of intraspinal tumor extension, relationship between the major vessels and the tumor .

19. Screening Started in Japan & has been there since 20 years. Patients diagnosed with screening have uniform survival of >97%. Before screening, 20% diagnosis before age 1 which increased to 55% after screening implementation. However, the number of children older than 1 year of age diagnosed with advanced-stage disease has not decreased . Biologic differences between tumors diagnosed by screening and those detected clinically.

20. Staging

21. Treatment Surgery , chemotherapy, and radiation therapy . The role of each in individual patients varies depending on tumor stage, age, and biologic prognostic factors.

22. Low-Risk Disease (Stages I, II, and IV-S). Children with stage I neuroblastoma have a disease-free survival rate of greater than 90% with surgical excision alone Chemotherapy is indicated only in the event of recurrence unless the child has MYCN amplification and unfavorable histology . Radiation therapy has no role in this subset of patients .

23. Intermediate and High-Risk Disease (Stages III and IV). Chemotherapy Surgery Usually the safest approach for advanced tumors is to defer resection until after initial chemotherapy. The tumors are smaller and firmer, with less risk of rupture and hemorrhage after chemotherapy , resulting in a decreased rate of complications, particularly nephrectomy.

24. Surgery usually is performed 13 to 18 weeks after initiation of chemotherapy, allowing three to four courses of treatment. Extensive surgical resection can result in Diarrhoea & Chylus acities .

25. RADIOTHERAPY Radiotherapy has a role in neuroblastoma because tumor is radiosensitive.it is most useful in achieving local control and palliation of disease uncontrollable by other modalities. DOSE= Ranged b/w 15 and 30 Gy

26. New Innovative Biologic Therapies Double autologous bone marrow transplantation. Has allowed the use of myeloablative therpies . Multiple monoclonal antibodies.

27. Wilms tumor Wilms tumor , or nephroblastoma , is the most common primary malignant renal tumor of childhood. It is an embryonal tumor that develops from remnants of immature kidney.

28. Epidemiology Wilms tumor accounts for approximately 6% to 7% of all childhood cancers. It is the most common renal tumor of childhood, accounting for 95% of all kidney cancers in children under the age of 15 in the United State. Incidence rate of Wilms tumor is 8.0 per million. More than 80% of cases are diagnosed before 5 years of age, with a median age of 3.5 years. It is lower in bilateral cases & in children with syndromic predisposition. Incidence in East A sian population is lower than black population.

29. Genitics Wilms tumor Sporadic familial Early age, B/L WTI(11p13)10% WT2(11p15)4% LOH 16q (20%) WTX(30%) Mutation. DDS LOS BWS risk of relpase same pathway as WTI Deltion . WAGR LOH 1p (10%) risk of relpase combined loss will result in worse replase

30. Clinical presentation Most common presentation is abdominal mass. Haematuria 20%. Gross haematuria warrants further workup. Anorexia, weight loss, malaise 10% Hypertension 20-25% Asymptomatic Atypical presentation . Persistent vericocele , hepatomegaly, CCF.

31. Examination Head to toe examination is imp Exclude associated condition BP

32. Labs CBC, S/E, LFTS, RFTs, S.calcium Coagulation profile. As 8% of newly diagnosed patients have acquired von Willebrand disease.

33. Diagnosis Ultrasound solid mass of the kidney Doppler ultrasound can determine vena caval involvement. Give good idea of association with spleen, liver & other solid organs.

34. Triphasic CT Should be chest,abdomen & pelvis Arterial, venous & excretory phase CT chest. Lung is the most common site for distant metastasis MRI. Same as CT but require sedation or anaesthesia in children

35. Staging The most important determinants of outcome in children with Wilms tumor are the histopathology and tumor stage .

36. Management Multidisciplinary team work Surgeon Radiologist pathologist Oncologist Radiotherapist Geneticist

37. Two management arms NWTGS/COG SIOP Surgery > pre op chemo Followed by chemo, > followed by surgery XRT >further chemo or Pre op chemo only in radio if needed selected cases. The overall survival in both groups is >90% in low stage tumor & >80% in high stage tumor

38. Advantages & disadvantages NWTGS/COG SIOP Advantages disadvantages Accurate histology Increase d risk of surgical complications Benign vs malignant Chances of tumor spillage Accurate stage Failure to sample node leads to under treatment Advantages disadvantages Fever surgical complications Modification of yumor histology Lower incidence of tumor rupture Loss of staging information Asses tumor response Chemotherapy in a benign disease Downstaging of patient Chemotherapy to a different malignant tumor Possible role of renal sparing surgery in the affected kidney International Version. No biopsy UK version. Pre chemo biopsy

39. Neoadjuvant chemotherapy Local disease . 4 weeks, 2 drugs( actinomycin , Vincristine) Metastatic disease . 6 weeks,3 drugs( Act,VCR , Dox ) Special situations . B/L tumor tumor in solitory kidney horse shoe kidney Where the oncologist can modify the chemo.

40. Surgery Role of the surgeon Before surgery the surgeon must know. ???? surgical approach Laparoscopic surgery. In selected cases.

41. Lymph nodes 7 locoregional lymph nodes shpuld be sampled. Hilar & paraaortic lymph node should be sampled even if not suspicious. Involved lymph node should be excised. Radical lymph node dissection is not recommended. Post chemo necrotic lymph node should be considered positive.

42. Role of nephron sparing surgery.

43. After surgery Histolgy Percentage of necrosis 100% Complete necrosis 66-99% Regressive type <66% Histological subtypes Balstemal stromal epithelial Mixed Diffuse anaplasia

44. SIOP protocols Intermediate risk

45. NWTSG protocols Favourable hostology Unfavurable Histology Epithelial predominant Diffuse anaplasia S tromal predominant Focal anaplasia B lastemal predominant

46. COG protocols Stage & histology Surgery Chemotherapy Radiation therapy I or II favourable histo without LOH at 1p & 16q Nephrectomy Vancristine , Actinmomycin -D No I or II favourable histo withLOH at 1p & 16q Nephrectomy Vancristine , Actinmomycin -D, Doxurubicin No III & IV favourable histo without LOH at 1p & 16q Nephrectomy Vancristine , Actinmomycin -D, Doxurubicin Yes III & IV favourable histo with LOH at 1p & 16q Nephrectomy Vancristine , Actinmomycin -D, Doxurubicin Cyclophosphamide, Etoposide Yes

47. COG high risk group management Focal anaplastic stage I-III Wilms tumors and diffuse anaplastic stage I Wilms tumors Nephrectomy followed by vincristine, actinomycin -D, and doxorubicin in addition to local radiotherapy. Focal anaplastic stage IV Wilms tumors and diffuse anaplastic stage II-III tumors Patients undergo the same treatment, with the addition of cyclophosphamide, etoposide , and carboplatin. Stage IV diffuse anaplastic Wilms tumors More aggressive treatment is delivered; nephrectomy is followed by initial irinotecan and vincristine administration, which in turn is followed by actinomycin -D, doxorubicin, cyclophosphamide, carboplatin, etoposide , and radiotherapy.

48. B/L wilms tumor Synchronous bilateral Wilms tumors occur in 5% to 7% of children with Wilms tumor . Children with bilateral tumors should not undergo initial radical nephrectomy. These children should receive preoperative chemotherapy with the goal of tumor shrinkage and renal-sparing surgery Pre chemo for 6 weeks. Responders can be allowed for surgery. Non responder should B/L open renal biopsy.

49. If nephron sparing surgery is not feasible then additional chemo is given based on biopsy report. 2 drugs initially, if poor response then 3 drugs. All patients are recommended to undergo surgical resection within 12 weeks of therapy. Can undergo partial nephrectomies on both sides or radical on one & partial on other side. Rarely b/l nephrectomies

50. Follow up General well being & growth of the child Ultrasound Chest x ray Yearly serum creatinine if renal function is normal Three monthly creatinine & S/E if renal dysfunction Yearly urine R/E for protienuria

51. Thank you