1. Radiotherapy in Renal Cell Carcinoma Simin Hemati. M.D Assistant professor of Radiation Oncology Isfahan University of Medical Sciences 20 jan 2012

2. RCC is the most common type ( 80% ) of kidney cancer in adults, It is also known to be the most lethal of all the genitourinary tumors

3. American Joint Committee on Cancer Staging Classification for Kidney Tumors 7 th edition 2010

4. Primary Tumor Description TXPrimary tumor cannot be assessed T0No evidence of primary tumor T1Tumor 7 cm in greatest dimension, limited to the kidney T1aTumor 4 cm or less in greatest dimension, limited to the kidney T1bTumor more than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney T2Tumor more than 7 cm in greatest dimension, limited to the kidney T2aTumor more than 7 cm but less or equal to 10 cm T2bTumor more than 10 cm limited to kidney T3Tumor extends into major veins or perinephric tissues but not to epsilateral adrenal gland and not beyond Gerota's fascia T3aTumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumor invades perirenal and or renal sinus fat but not beyond Gerota's fascia T3bTumor grossly extends in to the vena cava below the diaphragm T3cTumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava T4Tumor invades beyond Gerota's fascia(including epsilateral adrenal gland)

5. American Joint Committee on Cancer Staging Classification for Kidney Tumors Regional Lymph Nodes Description NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis to regional lymph node

6. American Joint Committee on Cancer Staging Classification for Kidney Tumors Distant MetastasisDescription MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

7. Stage Grouping STAGEDescription I T1 N0M0 II T2N0M0 III T3 T1,T2 N0 N1 M0 IV T4 Any T Any N M0 M1

8. Histopathologic Grade GRADEDescription GXGrade cannot be assessed G1Well differentiated G2Moderately well differentiated G3,G4Poorly differentiated or undifferentiated

9. Stage of Renal Cell Carcinoma Correlated with Survival After Radical Nephrectomy AuthorNo of patient IIIIIIIV Robson et al. 8866644211 Skinner et al. 30965 47 518 Waters and Richie 130 51 59 120 McNichols et al. 50667513414 Selli et al. 11593638013 Golimbu et al. 3268867402 Dinney et al. 31473685120 Guinan et al. 337 10096 5916 Javidan et al. 38195885910 Kinouchi et al. 3509695 70 24 Tsui et al. 643917467 32

10. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment.nephrectomy

11. Adenocarcinoma of the kidney is a variably radiosensitive neoplasm.

12. Huland and et all: Radiotherapy before surgery decreased the rate of tumor transplantation some renal cell cancer are resistant to conventionally fractionated RT Other studies : In vivo experiments

13. Clinical experiences Palliative RT in advanced stage very good subjective and objective response No improved the results Adjuvant RT in early stage

14. Post operative radiotherapy Palliative radiotherapy Pre opreative radiotherapy Rt in RCC

15. Pre operative RT Pre operative RT Theoretical Benefits : Theoretical Benefits :  tumor shrinkage  increased resectability  decreased tumor viability with fewer distant metastases

16. Two European studies Nephrectomy alone Preoperative RT + nephrectomy No improved in overall survival No improved in free metastatic survival Increased resectability in T2, T3 Tumors No improved in overall survival No improved in free metastatic survival Increased resectability in T2, T3 Tumors

17. Preoperative irradiation should be considered in patients with technically unresectable nonmetastatic tumors to convert them to resectable.

18. Post operative RT

19. A retrospective review from Memorial Sloan-Kettering Cancer Center of 172 patients treated by radical nephrectomy alone T1 or T2 tumors,N0 Local failure is 4% Local failure is 21% LN positive or positive margin

20. A retrospective series with 67 patient of T3 tumors 37 30 Nephrectomy + post operative RT Local failure is 10% Local failure is 37% Nephrectomy alone Nephrectomy alone

21. Indications of post operative RT gross or microscopically positive margins gross or microscopically positive margins LN positive LN positive Locally advanced tumors (T3,T4) Locally advanced tumors (T3,T4)

22. Patients with renal cell carcinoma confined to the kidney and/or renal vein have a low recurrence rate and a high survival rate after radical nephrectomy alone and should not be considered for adjuvant radiation therapy.

23. At diagnosis, 30% of renal cell carcinomas have spread to the ipsilateral renal vein Complete Resection NO RTX

24. Palliative radiotherapy for relief from symptoms after surgery for metastatic lesion Palliative radiotherapy : for relief from symptoms pain neorologic symptoms spinal cord compression nerve invasion after surgery for metastatic lesion

25. Radiation therapy technique

26. Preoperative RT Preoperative RT Total dose : 45-50 GY Target volume : kidney and regional LN Technique : two POP technique two POP technique multiple technique similar to post operative setting multiple technique similar to post operative setting

27. Post operative RT

28. 45 to 50 Gy 1.8 to 2Gy F To kidney bed and regional lymph nodes 45 to 50 Gy 1.8 to 2Gy F To kidney bed and regional lymph nodes total dose 50 to 60 Gy 10-15 GY boost to small volumes of microscopic or gross residual If the scar cannot be covered without increasing the amount of normal tissue irradiated, an additional electron beam field to treat the scar may be considered.

29. Radiation Oncologists must be attention to: Patient selection Radiation therapy planning Tolerance of the upper-abdominal organs

30. Tolerance dose of : Tolerance dose of : Liver : no more than 30% of the liver from Liver : no more than 30% of the liver from receiving doses >36 to 40 Gy receiving doses >36 to 40 Gy Spinal Cord : <45 Gy Spinal Cord : <45 Gy

31. Techniques: Anterior-Posterior technique: Anterior-Posterior technique: particularly on the right side, irradiated of large volumes of bowel and liver beyond tolerance. Multiple-beam technique: Multiple-beam technique: including anterior, posterior, oblique, and lateral projections with beam's eye-view shaping and differential weighting of dose from each field, can optimize the radiation dose distribution to maximize target volume coverage while minimizing the dose to normal bowel or liver including anterior, posterior, oblique, and lateral projections with beam's eye-view shaping and differential weighting of dose from each field, can optimize the radiation dose distribution to maximize target volume coverage while minimizing the dose to normal bowel or liver

32. The use of 3D-CRT and IMRT: The use of 3D-CRT and IMRT: Increased the tumor total dose Decreased the normal tissue dose

33. A CT–based treatment plan using a combination of four fields (anterior, posterior, right lateral, and right posterior oblique) to cover the tumor bed (dark oval) with 54 Gy (isodose line displayed). This combination of fields and beam's-eye-view shaping allows sparing of the liver, bowel, and spinal cord. LAT. OBL. POST ANT RT- LAT

34. Palliative RT techniques EBRT : EBRT : Treatment fields: metastatic foci with 2- 3cm margins. Treatment fields: metastatic foci with 2- 3cm margins. Dose: 35 - 40 Gy (symptomatic relief in 65% to 85% of patients). Dose: 35 - 40 Gy (symptomatic relief in 65% to 85% of patients). Some series have reported higher symptomatic response rates with higher irradiation dose( 45 to 50 Gy in 3 to 4.5 weeks) Some series have reported higher symptomatic response rates with higher irradiation dose( 45 to 50 Gy in 3 to 4.5 weeks)

35. Palliative RT techniques Stereotactic radiosurgery : Stereotactic radiosurgery : has been successful at controlling and palliating metastatic sites. 69 patients with brain metastases 33% stable 63% Responded

37. Initial treatment is most commonly a Radical or Partial NephrectomyNephrectomy And remains the mainstay of curative treatment

38. Complications of RT  nausea, vomiting, diarrhea, and abdominal cramping  radiation-induced liver damage  duodenum and small-bowel stenosis and bleeding  Spinal damage

39. Rate of complications related to: Rate of complications related to: Total dose Total dose Fraction size Fraction size Technique of irradiation Technique of irradiation