1. NEW ASPECTS OF ADJUVANT THERAPY IN ENDOMETRIAL CANCER (update of our current treatment policy) Zvi Bernstein M.D. ONCOLOGY DIVISION Rambam Health Care Campus Lin Oncology Staff Meeting, 08.01.2009
8. SURGICAL STAGING Lin Oncology Staff Meeting, “ Probably the most controversial aspect of this is the component of lymphadenectomy,” 08.01.2009
9. Lymphadenectomy (ACOG & ASGO,NCCN) Lin Oncology Staff Meeting, “ Complete dissection should be the gold standard!” “ 90% of involved nodes are only microscopically positive and the extent of dissection influences survival. ” 08.01.2009
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12. Number of Nodes Removed Over Time Lin Oncology Staff Meeting, Abu-Rustum et al. Gyn Oncol 103:714-718, 2006 08.01.2009
13. Lymphedema Risk vs. Number of Nodes Removed Lin Oncology Staff Meeting, Abu-Rustum et al. Gyn Oncol 103:714-718, 2006 08.01.2009
41. Lin Oncology Staff Meeting, NSGO EORTC A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991) On behalf of NSGO and EORTC T. Hogberg 1 , P. Rosenberg 1 , G. Kristensen 1 , CF de Oliviera 2 , R de Pont Christensen 1 B Sorbe 1 , C Lundgren 1 , H Andersson 1 , T Salmi 1 , NS Reed 2 . 1 Nordic Society of Gynecologic Oncology, Odense, Denmark, 2 Europ Org for Research and Treatment of Cancer, Brussels, Belgium. 08.01.2009
42. NSGO EC-9501/EORTC-55991 Radical surgery T AH+BSO (+PLA) RT+CT RT CT+RT OR Randomization Primary endpoint P rogression-free survival (PFS) Surgical stage I, II, IIIA ( positive peritoneal fluid cytology only), or IIIC (positive pelvic lymph nodes only) Endometrioid Type – 61% Serous, clear cell, or anaplastic carcinomas (39%) were eligible regardless of other risk factors 44 Gy XRT ± optional brachytherapy (BT:39%) CT : intially AP Later AP, TP, TAP, TEP 196 cases 186 cases 382 cases May 1996 to January 2007 (BT:44%) Lin Oncology Staff Meeting, 08.01.2009
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46. PORTEC – 2 Design TAH / BSO no LND Eligibility: High intermediate risk group -age>60+ IC G1-2 or IB G3 -stage IIa N=427 pts EBRT N=214 Brachytherapy N=213 Primary endpoint: rate of vaginal relapse Secondary endpoints: OS, QOL Lin Oncology Staff Meeting, 08.01.2009
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51. JGOG 2033 Randomized phase III trial of pelvic RT versus cisplatin-based chemotherapy in patients with intermediate risk endometrial carcinoma S. Sagae, N. Susumu, Y. Udagawa, K. Niwa, R. Kudo, S. Nozawa, for the Japan Gynecologic Oncology Group Gynecologic Oncology 108 (2008) 226–233 Lin Oncology Staff Meeting, 08.01.2009
58. 422 PTS. 202 – WAI, 194 - PA Lin Oncology Staff Meeting, 08.01.2009
59. Whole abdominal irradiation vs. doxorubicin/cisplatin (60/50) regimen for stage III/IV endometrial cancer (GOG #122) Lin Oncology Staff Meeting, 08.01.2009 Clinical data WAI CT No. of patients 202 194 No. of patients alive 38% 51% Treatment-related death 4 8 Deaths from cancer 100 78 60-Month PFS (corrected for stage) 38% 60% 60-Month survival (corrected for stage) 42% 55%
61. Conclusions Patients with surgical stage III or IV Endometrial Carcinoma treated with AP experienced a statistically significant improvement in survival when compared with patients who received WAI, but also experienced more frequent and more severe acute toxicity. Lin Oncology Staff Meeting, 08.01.2009
62. An overview about the performed CT phase-III trials of GOG in endometrial cancer Lin Oncology Staff Meeting, *more toxicity with PFS and OAS no superior to the current standard therapy 08.01.2009 Trial Regiment RR (%) PFS (mos) OS #107 Dox Dox/Cis 27 45 3.8 5.7 9.2 9.0 #139 Dox/Cis (AC) Circadian (AC) 46 49 6.5 5.9 11.2 13.2 #163 Dox/Cis Pac/Dox+GCSF 40 44 7.2 6.0 12.4 13.6 #177* Dox/Cis (60 45/50) Pac/Dox/Cis+GCSF (160/45/50)---TAP 34 57 5.3 8.3 12.1 15.3
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64. Surgically staged patients at least 8 LN evaluated (4 from each side of the Pelvis) Lin Oncology Staff Meeting, 08.01.2009
65. STAGE I Lin Oncology Staff Meeting, 08.01.2009 Stage Post-Operative Therapy IA, IB, IC Grades I and II No further therapy Chemotherapy if ≥ 2/3 Myometrial Invasion IA, IB, IC with Grade III or LVSI Vaginal cuff brachytherapy HDR 700 cGy at ½ cm X 3 Or HDR 350 cGy at ½ cm X 6 And Chemotherapy if ≥ 2/3 Myometrial Invasion
66. STAGE II Lin Oncology Staff Meeting, 08.01.2009 Stage Post-Operative Therapy IIA, IIB Vaginal cuff brachytherapy HDR 400 cGy at ½ cm X 6 Chemotherapy if ≥ 2/3 Myometrial Invasion
67. STAGE III Lin Oncology Staff Meeting, Groin irradiation is added if the disease involves the distal 1/3 of the vagina. Pelvic IMRT may be given with negative lymph nodes if the patient’s tumor has features of deep myometrial invasion, high grade, or extensive LVSI. 08.01.2009 Stage Post-Operative Therapy IIIA, IIIB Vaginal cuff brachytherapy HDR 350 cGy at ½ cm X 6 Chemotherapy if ≥ 2/3 Myometrial Invasion IIIC Pelvis only unless Para-Aortic Nodes Positive IMRT plus vaginal cuff brachytherapy 5,120 CTV Final And HDR 200 cGy at ½ cm X 6 (250 cGy for LVSI, 300 cGy for +/close margins) + Chemotherapy
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69. RESULTS (1) Lin Oncology Staff Meeting, Median follow-up was 27 months (range, 2–96 months). 08.01.2009
72. Incompletely surgically staged patients Lin Oncology Staff Meeting, Groin irradiation is added if the disease involves the distal 1/3 of the vagina. 08.01.2009 Stage Post-Operative Therapy IA, IB G1, 2 No further therapy I; G3 (Any myometrial invasion) IC (Any Grade) II, III (Any Grade) IMRT plus vaginal cuff brachytherapy 5,120 CTV Final And HDR 200 cGy at ½ cm X 6 HDR (250 for LVSI, 300 cGy X 6 for +/close margins) + Chemotherapy
73. THANK YOU ! 08.01.2009 Lin Oncology Staff Meeting,
