1. Training Module 8 – Version 1.1 For Internal Use Only ® Literature 

2. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

3. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature SIRT is often regarded as second, third or even fourth line treatment The more treatments failed, the worse is the prognosis for the patient Comparing survival rates can therefore sometimes be misleading Some words about patient collective beforehand: 

4. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature The response is usually measured either as an effect on a specific tumour marker (CEA or AFP) or as a decrease in the size of the lesion(s) It is known that the response (size of lesion) often seems to be delayed in CT, whereas a functional scan like PET shows quite quickly that there is a response Comparing response rates by tumour size can therefore sometimes be misleading Some words about response rate beforehand: CEA = carcinoembryonic antigen AFP = α-fetoprotein 

5. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Especially in older studies, HAC is used as the standard. But this local therapy does not treat any extrahepatic disease Often this extrahepatic disease mostly leads to the death of the patient rather than the secondary liver disease Comparing survival rates can therefore sometimes be misleading Some words about survival beforehand: 

6. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Median Survival – Kaplan Meier Plot The median survival is the time at which half the subjects have died. The example survival curve shows 50% survival at 5 months, so median survival is 5 months.

7. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Hazard – Kaplan Meier Plot The hazard is the slope of the survival curve – a measure of how rapidly subjects are dying.

8. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Hazard – Kaplan Meier Plot The hazard ratio compares two treatments. If the hazard ratio is 2.0, then the rate of deaths in one treatment group is twice the rate in the other group. If it is 0.33, the rate of death is one third of the rate in the other group. Treatment A Treatment B

9. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

10. Training Module 8 – Version 1.1 For Internal Use Only ® mCRC Clinical Studies Literature 

11. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Randomized trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastasis from primary large bowel cancer B.Gray, G. Van Hazel, M.Hope, M.Burton, P.Moroz, J.Anderson, V.Gebski Annals of Oncology 12:1711-1720, 2001 Phase III randomized trial (open for entry 1991-1997) SIR-Spheres plus hepatic artery chemotherapy via port 74 patients with bipolar non-resectable CRC metastasis Primary objectives: response, time to progression, survival, quality of life and toxicity 

12. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 SIRT within 4 weeks after port implantation Angiotensin injected prior to implant Randomization SIRT + HAC with FUDR 12 day cycle 4 weekly 18 cycles HAC with FUDR 12 day cycle 4 weekly 18 cycles n=34 n=36 n=70 4 patients weren't eligible 

13. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 CR=complete response, PR=partial response, NC=no change, PD= progressive disease, NA=not assessable 

14. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 CR=complete response, PR=partial response, NC=no change, PD= progressive disease, NA=not assessable 

15. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 CR=complete response, PR=partial response, NC=no change, PD= progressive disease, NA=not assessable 

16. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 

17. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 Kaplan-Meier: Survival 

18. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 

19. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001 Significant greater response rate Significant longer time to disease progression Increased survival No increased toxicity No loss of quality of life Risk of death from progression of liver metastasis was 3.1 times higher in the control group One patient treated with SIR-Spheres is considered permanently cured Study was basis for the pre-market approval of FDA (US) 

20. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature B.Gray et al, Annals of Oncology 12:1711-1720, 2001  Study closed prior to completion (95 patients planned)  Statistically the study with only 74 patients is not very powerful  Most patients died from extra-hepatic disease  Treatment regimen not suitable to treat any extra-hepatic disease 

21. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Randomized Phase 2 Trial of SIR-Spheres Plus Fluorouracil/ Leucovorin Chemotherapy Versus Fluorouracil/Leucovorin Chemotherapy Alone in Advanced Colorectal Cancer Guy Van Hazel, Anthony Blackwell, James Anderson, David Price, Paul Moroz, Geoff Bower, Guiseppe Cardaci, Bruce Gray Journal of Surgical Oncology 2004;88:78-85 Phase II trial with 21 patients Systemic chemotherapy with and without SIRT (femoral catheter) Patients with CRC liver metastasis with and without extra-hepatic disease Primary objectives: response, time to progression and toxicity 

22. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 SIRT 3 rd or 4 th day of 2 nd cycle Angiotensin injected prior to implant Randomization SIRT + Systemic Chemo 5-FU/Leucovorin 5 day cycle 4 weekly until progression Systemic Chemo 5-FU/Leucovorin 5 day cycle 4 weekly until progression n=10 n=11 n=21 

23. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 Time to progressive disease 

24. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 Survival by treatment 

25. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Time to PD significantly longer for SIRT patients (18.6 month versus 3.6 month) Significant better median survival for SIRT patients (29.4 month versus 12.8 month) One SIRT patient still alive at date of publication G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 

26. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85  Small number of patients only However, the high response rate, long time to disease progression and survival suggest that adding SIRT to systemic chemotherapy can improve patient outcome. SIRFLOX Study 

27. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature FOLFOX 4 Dose Escalation Trial Guy Van Hazel et al ASCO GI 2005, Florida, USA Phase II trial with 20 patients Systemic chemotherapy with Oxaliplatin in combination with SIRT (femoral catheter) Patients with CRC liver metastasis Primary objectives: response and survival 

28. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature 2 patients with complete response, 16 with partial response and 2 with static disease. None with PD Median time to progression is currently 11.9 months For those with liver only disease the time to progression is currently 14.9 months Median survival cannot be determined at that stage G. Van Hazel et al, ASCO GI 2005, Florida, USA 

29. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Randomized Comparative Study Of FOLFOX6m Plus SIR-Spheres versus FOLFOX6m Alone As First Line Treatment In Patients With Non-Resectable Liver Metastasis From Primary Colorectal Carcinoma Peter Gibbs and Guy Van Hazel (Principal Investigator) Unpublished – Study open to accrual Trial with more than 300 patients Systemic chemotherapy with and without SIRT (femoral catheter) Patients with CRC liver metastasis with and without extra-hepatic disease Primary objectives: Progression free survival at any site and progression free survival in the liver 

30. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual soon SIRT 1 st week of 1 st cycle Randomization SIRT + Systemic Chemo Oxaliplatin Leucovorin 5-FU repeated 2 weekly Systemic Chemo Oxaliplatin Leucovorin 5-FU repeated 2 weekly n>150 n>300 

31. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Statistical powerful study State of the art chemotherapy regimen Multicentre study P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual 

32. Training Module 8 – Version 1.1 For Internal Use Only ® HCC 

33. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study W.-Y. Lau, W.-T. Leung, S. Ho, N.W.Y. Leung, M. Chan, J. Lin, C. Metreweli, P. Johnson and A.K.C. Li British Journal of Cancer 1994;70:994-999 Phase I and II trial with 18 patients Patients with inoperable HCC, recruited 90-93 SIRT via port Primary objectives: response and survival 

34. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999 Angiotensin injected prior to implant Randomization SIRT < 120Gy n=8 n=18 SIRT > 120Gy Angiotensin injected prior to implant 

35. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999 

36. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999 Significant better median survival for patients receiving the higher dose (55.9 versus 26.2 weeks) Dose of >120Gy is recommended Three SIRT patients still alive after 10.4, 17.2 and 27.4 month respectively 

37. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies Literature W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999  Small number of patients only However, the result clearly shows the advantage of a well dosed SIRT treatment. 

38. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Combined Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

39. Training Module 8 – Version 1.1 For Internal Use Only ® Literature Clinical Experience in mCRC Kennedy et al, USA, 208 patients Stubbs et al, NZ, 165 patients Gray et al, Aus, 71 patients Lim et al, Aus, 30 patients Poepperl et al, Germany, 23 patients Wong et al, USA, 19 patients Murthy, USA, 12 patients 

40. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Excellent overview on all published study data as well as clinical experience on both, glass spheres and SIR-Spheres 

41. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorGray et al. Year1989 Number of Patients10 Type of tumourmCRC TherapyY-90 alone Dose16.8-138.9Gy to normal liver Result8 of 9 with >50% reduction in CEA RemarksIntraoperative dosimetry 

42. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorGray et al. Year1992 Number of Patients29 Type of tumourmCRC TherapyY-90 ± HAC Dose755 – 4240 MBq Result 70% average decrease in pretreatment CEA 45% response rate based on CT RemarksNo significant toxicity 

43. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorGray et al. Year2000 Number of Patients71 Type of tumourmCRC TherapyY-90 + HAC DoseAverage activity 2130MBq Result 85% overall response rate Median survival 13.5 months RemarksFatal radiation hepatitis in one patient 

44. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorGray et al. Year2001 Number of Patients74 Type of tumourmCRC TherapyHAC ± Y-90 Dose2000 – 3000MBq Result 72% overall response rate versus 47% (HAC) 40% higher death rate in HAC alone RemarksPhase III randomized trial 

45. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorStubbs et al. Year2001 Number of Patients50 Type of tumourmCRC TherapyY-90 + HAC Dose2000 – 3000MBq Result Median survival 24.7 / 11.4 months (without extrahepatic / with extrahepatic disease) RemarksDuodenal ulceration in six patients 

46. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorStubbs et al. Year2003 Number of Patients100 (including 50 published earlier) Type of tumourmCRC TherapyY-90 + HAC Dose2000 – 3000MBq Result Median survival 12.6 / 8.3 months (without extrahepatic progression / with extrahepatic progression at 6 month) RemarksFatal radiation hepatitis in one patient 

47. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorVan Hazel et al. Year2004 Number of Patients21 Type of tumourmCRC TherapyY-90 + Systemic Chemotherapy Dose1500 – 2500MBq Result Time to progression 18.6 months versus 3.6 months Remarks Phase III randomized trial Radiation hepatitis in one patient 

48. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorMurthy et al. Year2005 Number of Patients12 Type of tumourmCRC TherapyY-90 + Systemic Chemotherapy DoseMedian dose 39.6mCi Result 4/7 patients with response on CEA levels 5/12 patients with stable radiologic response Remarks Treatment after failure of multiple chemotherapy regimens Gastric ulceration in one patient 

49. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorWong et al. Year2005 Number of Patients19 Type of tumourMET (metastatic) TherapyY-90 alone DoseMedian dose 76Gy Result15 of 19 patients with metabolic response (PET) Remarks 

50. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorLim et al. Year2005 Number of Patients32 / 5 Type of tumourmCRC / HCC TherapyY-90 + Systemic Chemotherapy DoseUnavailable Result12 of 43 patients with partial response (CT) RemarksSevere gastric ulceration in four patients 

51. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Is there a common pattern of results? No: All results seem to be different, because:  different patient collectives  different outcome measurements Yes: Irregardless of patient collective and outcome measurements, all SIRTEX patients are doing extraordinary well! 

52. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

53. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Excellent overview on all published study data as well as clinical experience on both, glass spheres and SIR-Spheres 

54. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorLau et al. Year1994 Number of Patients18 Type of tumourHCC TherapyY-90 alone Dose26-409Gy to tumour Result 50% partial response by CT scan 100% response by AFP or ferritin levels Median survival 55.9 weeks RemarksSignificant better survival in patients >120Gy 

55. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorLau et al. Year2001 Number of Patients82 Type of tumourHCC TherapyY-90 alone DoseMedian cumulative dose 332Gy and 268Gy Result Median survival 21.0 months (332Gy) Median survival 4.5 months (268Gy) Remarks 

56. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 AuthorMurthy et al. Year2005 Number of Patients12 Type of tumourmCRC TherapyY-90 + Systemic Chemotherapy DoseMedian dose 39.6mCi Result 4/7 patients with response on CEA levels 5/12 patients with stable radiologic response Remarks Treatment after failure of multiple chemotherapy regimens Gastric ulceration in one patient 

57. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

58. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature G. Poepperl et al. Cancer Biotherapy & Radiopharmaceuticals 2005;20:200-208 AuthorPoepperl et al. Year2005 Number of Patients12 / 4 / 2 / 1 / 1 / 2 Type of tumourCRC/Breast/Pancreas/Melanoma/NET/ HCC TherapyY-90 + Systemic Chemotherapy prior to SIRT DoseMean activity: 2270MBq Result Promising responses, long term survival data to be published Remarks Mild pancreatitis and gastric ulceration in one patient each 

59. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature D. Rubin et al. Integrative Cancer Therapies 2004;3:262-267 AuthorRubin et al. Year2004 Number of Patients1 Type of tumourMetastatic Breast Cancer TherapyY-90 + Systemic Chemotherapy prior to SIRT Dose- ResultStable disease after 13 months Remarks 

60. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature D. Coldwell et al. Society of Interventional Radiology (SIR) conference AuthorColdwell et al. Year2005 Number of Patients34 Type of tumourMetastatic Breast Cancer TherapyY-90 DoseAverage dose 1.75GBq Result 100% response (PET-Scan) 30/34 still alive after 10 months Remarks All patients report palliation of liver related symptoms 

61. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature D. Coldwell et al. World Congress on Gastrointestinal Cancer AuthorColdwell et al. Year2005 Number of Patients84 Type of tumourMetastatic Neuroendocrine Tumours TherapyY-90 DoseAverage dose 1000Gy to tumour volume Result 67% response (PET-Scan) Symptom relief in symptomatic patients Remarks14 cases of grade 3 GI toxicity 

62. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature A. Kennedy et al. International Congress on Anti-Cancer Treatment AuthorKennedy et al. Year2005 Number of Patients40 Type of tumourMetastatic Neuroendocrine Tumours TherapyY-90 (Thera-Spheres or SIR-Spheres) DoseAverage dose 36.59mCi (SIR-Spheres) Result3 CR, 3 SD, 34 PR RemarksFollow-up 2-48 months with 7 patients dod dod = dead of disease 

63. Training Module 8 – Version 1.1 For Internal Use Only ® Published outcome data Literature J. King et al. World Congress on Gastrointestinal Cancer AuthorKing et al. Year2005 Number of Patients22 Type of tumourMetastatic Neuroendocrine Tumours TherapyY-90 Dose- Result Radiological response (RECIST) at one month: 3 PR, 12 SD, 1 PD, 2 PR in one lobe Remarks2 patients dod at 4 and 7 months dod = dead of disease 

64. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

65. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature a MUST to READ 

66. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Murthy et al, RadioGraphics 2005; 25:41-55 

67. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Murthy et al, RadioGraphics 2005; 25:41-55 SIRT therapy principles Thera-Spheres ® versus SIR-Spheres ® Patient selection criteria Therapy planning and workup Clinical outcomes Complications 

68. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature a MUST to READ 

69. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Salem et al, J Vasc Interv Radiol 2006; 17:1251-1278 Technical and methodological considerations Patient screening and selection Vascular anatomy Treatment process Thera-Spheres ® and SIR Spheres ® 

70. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature a MUST to READ 

71. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Salem et al, J Vasc Interv Radiol 2006; 17:1425-1439 Special Topics Patient selection Complications Lobar versus whole liver approach Treating patients after other other treatments Combination with other treatments Workup and treatment the same day? Patients with increased lung shunting Long-term follow up 

72. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Shows the high degree of variation in the anatomy of the hepatic arterial bed and the consequences with regard to SIRT a MUST to READ 

73. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Liu et al, J Vasc Interv Radiol 2005, 16:911-935 

74. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Shows clearly that an early response on a treatment with SIR-Spheres can be detected by PET scanning but not by CT. 

75. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Szyszko et al, Nuclear Medicine Communications 2007, 28:15-20 PET CT before treatment after treatment 

76. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Points out the importance of a proper work-up, gives a quite good perspective on likelihood of side effects and how to deal with those 

77. Training Module 8 – Version 1.1 For Internal Use Only ® Mode of Action and Procedure Literature Further publications on: Blood supply of hepatic metastasis Dose calculation via partition model Microsphere and dose distribution within the liver Intraoperative dosimetry Pathologic response Responses on PET and CT scan 

78. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

79. Training Module 8 – Version 1.1 For Internal Use Only ® Radiation Protection Literature 

80. Training Module 8 – Version 1.1 For Internal Use Only ® Radiation Protection Literature Radiation Protection in Australia Series 4, 2002 Dose limits and dose constrains The discharge of patients following treatment Maximum dose rate at time of discharge Maximum activity to be administered to an outpatient Use of public transport by the patient 

81. Training Module 8 – Version 1.1 For Internal Use Only ® Radiation Protection Literature Gives a good overview of all radiation safety aspects including exposure and doses 

82. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

83. Training Module 8 – Version 1.1 For Internal Use Only ® Issues of Concern Literature Publications on: Portal hypertension after SIRT Radiation induced ulceration of the stomach Radiation pneumonitis Extra-hepatic embolization Serum proinflammatory cytokine response 

84. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

85. Training Module 8 – Version 1.1 For Internal Use Only ® Literature  a MUST to READ

86. Training Module 8 – Version 1.1 For Internal Use Only ® Review article Literature There are at least 15 further review article available Highly recommended 

87. Training Module 8 – Version 1.1 For Internal Use Only ® Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature 

88. Training Module 8 – Version 1.1 For Internal Use Only ® Liver Cancer What is most important to remember? All clinical studies with outcome Clinical experience published Overview to answer specific questions 

89. Training Module 8 – Version 1.1 For Internal Use Only ® RECIST criteria Literature Complete Response (CR) Disappearance of all known lesions on radiological grounds and normalization of AFP for at least 4 weeks Partial Response (PR) Decrease of 50% or more in the tumour volume and/or a decrease of more than 50% in AFP or ferritin level for at least 4 weeks Static Disease (SD) Decrease of tumour volume of less than 50% or an increase in tumour volume of not more than 25% Progressive Disease (PD) Increase of tumour volume of more than 25% or the appearance of a new lesion

90. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Median Survival – Kaplan Meier Plot The median survival is the time at which half the subjects have died. The example survival curve shows 50% survival at 5 months, so median survival is 6 months.

91. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Hazard – Kaplan Meier Plot The hazard is the slope of the survival curve – a measure of how rapidly subjects are dying.

92. Training Module 8 – Version 1.1 For Internal Use Only ® Definitions Literature Hazard – Kaplan Meier Plot The hazard ratio compares two treatments. If the hazard ratio is 2.0, then the rate of deaths in one treatment group is twice the rate in the other group. If it is 0.33, the rate of death is one third of the rate in the other group.