B.Gray et al
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Literature ® Training Module 8 – Version 1.1 Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Published outcome data Some words about patient collective beforehand: 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 Literature ® Training Module 8 – Version 1.1 Published outcome data Some words about response rate beforehand: 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 CEA = carcinoembryonic antigen AFP = α-fetoprotein Literature ® Training Module 8 – Version 1.1 Published outcome data Some words about survival beforehand: 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 Literature ® Training Module 8 – Version 1.1 Definitions 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. Literature ® Training Module 8 – Version 1.1 Definitions Hazard – Kaplan Meier Plot The hazard is the slope of the survival curve – a measure of how rapidly subjects are dying. Literature ® Training Module 8 – Version 1.1 Definitions Hazard – Kaplan Meier Plot Treatment A Treatment B 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. Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies B.Gray et al, Annals of Oncology 12:1711-1720, 2001 n=70 Randomization 4 patients weren't eligible n=36 n=34 HAC with FUDR SIRT + • 12 day cycle HAC with FUDR • 4 weekly • 12 day cycle • 18 cycles • 4 weekly • 18 cycles SIRT within 4 weeks after port implantation Angiotensin injected prior to implant Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies B.Gray et al, Annals of Oncology 12:1711-1720, 2001 Literature ® Training Module 8 – Version 1.1 Clinical Studies B.Gray et al, Annals of Oncology 12:1711-1720, 2001 Kaplan-Meier: Survival Literature ® Training Module 8 – Version 1.1 Clinical Studies B.Gray et al, Annals of Oncology 12:1711-1720, 2001 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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) Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 n=21 Randomization n=11 n=10 Systemic Chemo SIRT + • 5-FU/Leucovorin Systemic Chemo • 5 day cycle • 5-FU/Leucovorin • 4 weekly • 5 day cycle • until progression • 4 weekly • until progression SIRT 3rd or 4th day of 2nd cycle Angiotensin injected prior to implant Literature ® Training Module 8 – Version 1.1 Clinical Studies G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 Time to progressive disease Literature ® Training Module 8 – Version 1.1 Clinical Studies G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 Survival by treatment Literature ® Training Module 8 – Version 1.1 Clinical Studies G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies G. Van Hazel et al, ASCO GI 2005, Florida, USA 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual soon n>300 Randomization n>150 n>150 Systemic Chemo SIRT + • Oxaliplatin Systemic Chemo • Leucovorin • Oxaliplatin • 5-FU • Leucovorin • repeated 2 weekly • 5-FU • repeated 2 weekly SIRT 1st week of 1st cycle Literature ® Training Module 8 – Version 1.1 Clinical Studies P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual Statistical powerful study State of the art chemotherapy regimen Multicentre study ® Training Module 8 – Version 1.1 HCC Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999 n=18 Randomization n=8 n=8 SIRT SIRT < 120Gy > 120Gy Angiotensin injected prior to implant Angiotensin injected prior to implant Literature ® Training Module 8 – Version 1.1 Clinical Studies W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies 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. Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Combined Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 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 Literature ® Training Module 8 – Version 1.1 Published outcome data Excellent overview on all published study data as well as clinical experience on both, glass spheres and SIR-Spheres Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Gray et al. Year 1989 Number of Patients 10 Type of tumour mCRC Therapy Y-90 alone Dose 16.8-138.9Gy to normal liver Result 8 of 9 with >50% reduction in CEA Remarks Intraoperative dosimetry Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Gray et al. Year 1992 Number of Patients 29 Type of tumour mCRC Therapy Y-90 ± HAC Dose 755 – 4240 MBq Result 70% average decrease in pretreatment CEA 45% response rate based on CT Remarks No significant toxicity Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Gray et al. Year 2000 Number of Patients 71 Type of tumour mCRC Therapy Y-90 + HAC Dose Average activity 2130MBq Result 85% overall response rate Median survival 13.5 months Remarks Fatal radiation hepatitis in one patient Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Gray et al. Year 2001 Number of Patients 74 Type of tumour mCRC Therapy HAC ± Y-90 Dose 2000 – 3000MBq Result 72% overall response rate versus 47% (HAC) 40% higher death rate in HAC alone Remarks Phase III randomized trial Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Stubbs et al. Year 2001 Number of Patients 50 Type of tumour mCRC Therapy Y-90 + HAC Dose 2000 – 3000MBq Result Median survival 24.7 / 11.4 months (without extrahepatic / with extrahepatic disease) Remarks Duodenal ulceration in six patients Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Stubbs et al. Year 2003 Number of Patients 100 (including 50 published earlier) Type of tumour mCRC Therapy Y-90 + HAC Dose 2000 – 3000MBq Result Median survival 12.6 / 8.3 months (without extrahepatic progression / with extrahepatic progression at 6 month) Remarks Fatal radiation hepatitis in one patient Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Van Hazel et al. Year 2004 Number of Patients 21 Type of tumour mCRC Therapy Y-90 + Systemic Chemotherapy Dose 1500 – 2500MBq Result Time to progression 18.6 months versus 3.6 months Remarks Phase III randomized trial Radiation hepatitis in one patient Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Murthy et al. Year 2005 Number of Patients 12 Type of tumour mCRC Therapy Y-90 + Systemic Chemotherapy Dose Median 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 Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Wong et al. Year 2005 Number of Patients 19 Type of tumour MET (metastatic) Therapy Y-90 alone Dose Median dose 76Gy Result 15 of 19 patients with metabolic response (PET) Remarks Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Lim et al. Year 2005 Number of Patients 32 / 5 Type of tumour mCRC / HCC Therapy Y-90 + Systemic Chemotherapy Dose Unavailable Result 12 of 43 patients with partial response (CT) Remarks Severe gastric ulceration in four patients Literature ® Training Module 8 – Version 1.1 Published outcome data 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! Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Published outcome data Excellent overview on all published study data as well as clinical experience on both, glass spheres and SIR-Spheres Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Lau et al. Year 1994 Number of Patients 18 Type of tumour HCC Therapy Y-90 alone Dose 26-409Gy to tumour Result 50% partial response by CT scan 100% response by AFP or ferritin levels Median survival 55.9 weeks Remarks Significant better survival in patients >120Gy Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Lau et al. Year 2001 Number of Patients 82 Type of tumour HCC Therapy Y-90 alone Dose Median cumulative dose 332Gy and 268Gy Result Median survival 21.0 months (332Gy) Median survival 4.5 months (268Gy) Remarks Literature ® Training Module 8 – Version 1.1 Published outcome data Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193 Author Murthy et al. Year 2005 Number of Patients 12 Type of tumour mCRC Therapy Y-90 + Systemic Chemotherapy Dose Median 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Published outcome data G. Poepperl et al. Cancer Biotherapy & Radiopharmaceuticals 2005;20:200-208 Author Poepperl et al. Year 2005 Number of Patients 12 / 4 / 2 / 1 / 1 / 2 Type of tumour CRC/Breast/Pancreas/Melanoma/NET/ HCC Therapy Y-90 + Systemic Chemotherapy prior to SIRT Dose Mean activity: 2270MBq Result Promising responses, long term survival data to be published Remarks Mild pancreatitis and gastric ulceration in one patient each Literature ® Training Module 8 – Version 1.1 Published outcome data D. Rubin et al. Integrative Cancer Therapies 2004;3:262-267 Author Rubin et al. Year 2004 Number of Patients 1 Type of tumour Metastatic Breast Cancer Therapy Y-90 + Systemic Chemotherapy prior to SIRT Dose - Result Stable disease after 13 months Remarks Literature ® Training Module 8 – Version 1.1 Published outcome data D. Coldwell et al. Society of Interventional Radiology (SIR) conference Author Coldwell et al. Year 2005 Number of Patients 34 Type of tumour Metastatic Breast Cancer Therapy Y-90 Dose Average dose 1.75GBq Result 100% response (PET-Scan) 30/34 still alive after 10 months Remarks All patients report palliation of liver related symptoms Literature ® Training Module 8 – Version 1.1 Published outcome data D. Coldwell et al. World Congress on Gastrointestinal Cancer Author Coldwell et al. Year 2005 Number of Patients 84 Type of tumour Metastatic Neuroendocrine Tumours Therapy Y-90 Dose Average dose 1000Gy to tumour volume Result 67% response (PET-Scan) Symptom relief in symptomatic patients Remarks 14 cases of grade 3 GI toxicity Literature ® Training Module 8 – Version 1.1 Published outcome data A. Kennedy et al. International Congress on Anti-Cancer Treatment Author Kennedy et al. Year 2005 Number of Patients 40 Type of tumour Metastatic Neuroendocrine Tumours Therapy Y-90 (Thera-Spheres or SIR-Spheres) Dose Average dose 36.59mCi (SIR-Spheres) Result 3 CR, 3 SD, 34 PR Remarks Follow-up 2-48 months with 7 patients dod dod = dead of disease Literature ® Training Module 8 – Version 1.1 Published outcome data J. King et al. World Congress on Gastrointestinal Cancer Author King et al. Year 2005 Number of Patients 22 Type of tumour Metastatic Neuroendocrine Tumours Therapy Y-90 Dose - Result Radiological response (RECIST) at one month: 3 PR, 12 SD, 1 PD, 2 PR in one lobe Remarks 2 patients dod at 4 and 7 months dod = dead of disease Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure a MUST to READ Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure Murthy et al, RadioGraphics 2005; 25:41-55 Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure 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 Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure a MUST to READ Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure 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® Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure a MUST to READ Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure 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 Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure a MUST to READ Shows the high degree of variation in the anatomy of the hepatic arterial bed and the consequences with regard to SIRT Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure Liu et al, J Vasc Interv Radiol 2005, 16:911-935 Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure Shows clearly that an early response on a treatment with SIR-Spheres can be detected by PET scanning but not by CT. Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure Szyszko et al, Nuclear Medicine Communications 2007, 28:15-20 PET CT before treatment after treatment Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure 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 Literature ® Training Module 8 – Version 1.1 Mode of Action and Procedure 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 Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Radiation Protection Literature ® Training Module 8 – Version 1.1 Radiation Protection 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 Literature ® Training Module 8 – Version 1.1 Radiation Protection Gives a good overview of all radiation safety aspects including exposure and doses Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 Issues of Concern Publications on: Portal hypertension after SIRT Radiation induced ulceration of the stomach Radiation pneumonitis Extra-hepatic embolization Serum proinflammatory cytokine response Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Literature ® Training Module 8 – Version 1.1 a MUST to READ Literature ® Training Module 8 – Version 1.1 Review article There are at least 15 further review article available Highly recommended Literature ® Training Module 8 – Version 1.1 Clinical Studies mCRC HCC Other Cancer Mode of Action and Procedure Radiation Protection Issues of Concern Reviews Liver Cancer ® Training Module 8 – Version 1.1 What is most important to remember? All clinical studies with outcome Clinical experience published Overview to answer specific questions Literature ® Training Module 8 – Version 1.1 RECIST criteria 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 Literature ® Training Module 8 – Version 1.1 Definitions 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. Literature ® Training Module 8 – Version 1.1 Definitions Hazard – Kaplan Meier Plot The hazard is the slope of the survival curve – a measure of how rapidly subjects are dying. Literature ® Training Module 8 – Version 1.1 Definitions 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.
