Endometrial Carcinoma.Adjuvant Treatment

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NEW ASPECTS OF ADJUVANT THERAPY IN ENDOMETRIAL CANCER

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Endometrial Carcinoma.Adjuvant Treatment

  1. 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
  2. 2. EC FIGO STAGE Lin Oncology Staff Meeting, 08.01.2009
  3. 3. 2007: CLINICAL CANCER ADVANCES <ul><li>Major Clinical Cancer Advances in 2007- 6 major clinical cancer advances and a further 18 that are considered &quot;notable“, in independent annual review. </li></ul><ul><li>In Gynecologic Oncology: Only 1 finding was considered as &quot;notable&quot; advance: </li></ul><ul><ul><li>External-beam radiation does not improve outcomes in endometrial cancer. </li></ul></ul>Lin Oncology Staff Meeting, 08.01.2009
  4. 4. ASCO 2007 Comprehensive Conclusion: <ul><li>“ COMBINING EBRT WITH SURGERY </li></ul><ul><li>IS NOT EFFECTIVE AND WILL LIKELY END ANY DEBATE ABOUT CONTINUED USE EBRT FOR PATIENTS WITH ENDOMETRIAL CANCER” </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  5. 5. Introduction (1) <ul><li>EC usually diagnosed at early stage (up to 80% diagnosed as stage I , 13% with stage II ) </li></ul><ul><li>5-year OS as high as 88% in stage I disease. </li></ul><ul><li>Subgroups of patients with early stages have significantly decreased 5-OS rates, based on various prognostic factors, such as IC and grade 3 only a 5-OS of 66%. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  6. 6. Introduction (2) <ul><li>Endometrial cancer is often divided into 2 subtypes: </li></ul><ul><li>Type I etiologically related to unopposed estrogens and occurs mostly in hyperplasic endometrium and better prognosis. </li></ul><ul><li>Type II occurs mostly in atrophic endometrium with 3 atypical histological subtypes such as clear cell, papillary serous cancer (UPSC), and poor differentiated, and associated with high virulence, advanced stage at diagnosis and poor prognosis. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  7. 7. Introduction (3) <ul><li>Surgery is the primary treatment of both localized and advanced disease, the adequate surgical staging and pathological review are the prerequisites for any discussion about individual need for an adjuvant therapy </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  8. 8. SURGICAL STAGING Lin Oncology Staff Meeting, “ Probably the most controversial aspect of this is the component of lymphadenectomy,” 08.01.2009
  9. 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
  10. 10. Lymphadenectomy (FIGO) <ul><li>Pelvic LN sampling. </li></ul><ul><li>Para-aortic LN sampling indications: </li></ul><ul><li>-suspicious para-aortic or common iliac LN -grossly positive adnexa </li></ul><ul><li>-grossly positive pelvic LN </li></ul><ul><li>-full thickness myometrial invasion </li></ul><ul><li>-high grade tumors </li></ul><ul><li>-clear cell, serous papillary, carcinosracoma histologic subtype </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  11. 11. <ul><li>“ MORE SURGERY – LESS RADIOTHERAPY!” </li></ul>Lin Oncology Staff Meeting, 2000: TRENDY SLOGAN 08.01.2009
  12. 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. 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
  14. 14. NCCN GUIDELINES Lin Oncology Staff Meeting, 08.01.2009
  15. 15. Completely Surgically Staged Patient ? <ul><li>“ AT LEAST 8 LN </li></ul><ul><li>(4 FROM THE EACH </li></ul><ul><li>SIDE OF THE PELVIS)” </li></ul><ul><li>Perry W. Grigsby, M.D. </li></ul><ul><li>Mallinckrodt Institute of Radiology </li></ul><ul><li>Washington University </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  16. 16. Do Numbers Count? Lin Oncology Staff Meeting, 08.01.2009
  17. 17. Lin Oncology Staff Meeting, 467 patients 08.01.2009
  18. 18. Lin Oncology Staff Meeting, 509 patients 08.01.2009
  19. 19. Lymph Nodes Assessment Lin Oncology Staff Meeting, 08.01.2009
  20. 20. Risk Factors for Recurrence GOG#33 (1987) Prospective surgical-pathological study (1180 patients) <ul><li>Uterine Factors </li></ul><ul><li>Grade </li></ul><ul><li>Depth of MMI </li></ul><ul><li>LVS invasion </li></ul><ul><li>Cervical extension </li></ul><ul><li>Histologic type </li></ul><ul><li>Tumor location </li></ul><ul><li>Extrauterine Factors </li></ul><ul><li>Pelvic / PA nodes mts. </li></ul><ul><li>Adnexal mts. </li></ul><ul><li>+-ve peritoneal cytology (?) </li></ul><ul><li>Extension through serosa </li></ul><ul><li>Peritoneal implants </li></ul>Lin Oncology Staff Meeting, Morrow, Gyn Oncol 40:55-65,1991 08.01.2009
  21. 21. FIGO Degrees of Risk within Stage I EC GOG#33 (1987) Lin Oncology Staff Meeting, 08.01.2009
  22. 22. Lin Oncology Staff Meeting, 08.01.2009
  23. 23. GOG # 99 (2004) Lin Oncology Staff Meeting, 08.01.2009
  24. 24. GOG # 99 (2004) <ul><li>Complete surgical staging including pelvic and para-aortic node sampling </li></ul><ul><li>Surgical stage IB, IC, IIA (occult) and IIB (occult) </li></ul><ul><li>All histologic types except serous papillary and clear cell </li></ul><ul><li>Randomized to pelvic RT vs. no further therapy </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  25. 25. GOG # 99 (Patients) <ul><li>392 evaluable patients </li></ul><ul><li>58.5% IB, 32.1% IC, only 9.4% stage II(occult) </li></ul><ul><li>82.3% inner and middle third invasion, only </li></ul><ul><li>17.6% outer third invasion </li></ul><ul><li>81.6% grade 1 and 2, only 18.4% grade 3 </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  26. 26. GOG # 99 (Results) <ul><li>Recurrence Pattern Surgery Surgery+EBRT </li></ul><ul><li>Vagina, by randomization 13/172 (7.6%) 2/179 (1.1%) </li></ul><ul><li>Vagina, by treatment 15/172 (8.7%) 1/179 (0.6%) </li></ul><ul><li>received </li></ul><ul><li>Total pelvic failure, by 20/172 (12%) 3/179 (1.7%) </li></ul><ul><li>randomization </li></ul><ul><li>Total pelvic failure, by 22/172 (13%) 1/179 (0.6%) </li></ul><ul><li>treatment received </li></ul><ul><li>Surgery Surgery +EBRT </li></ul><ul><li>Alive (4 years) 86% 92% </li></ul><ul><li>Dead of disease 15/202 (7.4%) 8/190 (4.2%) </li></ul><ul><li>Intercurrent deaths 18/202 (8.9%) 14/190 (7.4%) </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  27. 27. PROBLEMS WITH GOG # 99 <ul><li>The number of events was smaller than expected and approximately 50% of deaths were due to intercurrent disease and the study was insufficiently powered to demonstrate a statistically significant survival difference. </li></ul><ul><li>Recognized during study that patient population being accrued was mostly low risk. Therefore, “low intermediate” and “high intermediate” risk groups were defined based on GOG #33 data base. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  28. 28. RISK GROUPS (1) GOG # 99 (2004) <ul><li>Low risk: </li></ul><ul><li>Grade 1–2 histology, with invasion through less than 50% of the myometrium. </li></ul><ul><li>Grade 3 without myometrial invasion. </li></ul><ul><li>Disease confined to the uterine fundus. </li></ul><ul><li>No lymphovascular involvement. </li></ul><ul><li>No evidence of metastases. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  29. 29. RISK GROUPS (2) GOG # 99 (2004) <ul><li>High-intermediate </li></ul><ul><li>Moderately-poorly differentiated tumor </li></ul><ul><li>Presence of LVSI </li></ul><ul><li>More than 50% myometrial invasion </li></ul><ul><li>Age > 50 with any 2 risk factors above </li></ul><ul><li>Age > 70 with any 1 risk factor </li></ul><ul><li>No evidence of metastases </li></ul><ul><li>Others considered “Low intermediate risk.” </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  30. 30. GOG # 99 (2004) <ul><li>Risk of recurrence at 2 year: </li></ul><ul><li>High intermediate risk ( 132 pts. ) - 27% </li></ul><ul><li>Low intermediate risk ( 260 pts. ) - 6% </li></ul>Lin Oncology Staff Meeting, GOG #33 (1987 ) 08.01.2009
  31. 31. RISK GROUPS (3) GOG # 99 (?) <ul><li>High risk: </li></ul><ul><li>Serosal involvement ( any Grade ) </li></ul><ul><li>Positive Peritoneal Cytology (IC Gr. 3) </li></ul><ul><li>Adnexal , pelvic or P/A metastases (any Grade and MMI) </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  32. 32. GOG #99: CONCLUSION <ul><li>Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a “high intermediate” risk definition. </li></ul><ul><li>Keys et al. Gynecol Oncol 2004; 92:744-751. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  33. 33. Lin Oncology Staff Meeting, 08.01.2009
  34. 34. Three important phase III randomized trials in 2007-2008 Lin Oncology Staff Meeting, 08.01.2009
  35. 35. Lin Oncology Staff Meeting, 08.01.2009
  36. 36. Trial design for ASTEC/EN.5 Surgery High risk pathology and no macroscopic disease RANDOMIZE No external beam RT External beam RT Primary endpoint: Overall survival Secondary endpoint: Recurrence-free survival 905 cases 453 cases 452 cases 2% EBRT, 51% Brachytherapy 98% EBRT, 52% Brachytherapy EN.5:   July 1996- ASTEC:   July 1998- 71% TAH BSO 29% TAH BSO PLN Lin Oncology Staff Meeting, 83% - Endometrioid 17% - SPC 29% - any LND 08.01.2009
  37. 37. Outcomes of ASTEC/EN.5 Lin Oncology Staff Meeting, 08.01.2009
  38. 38. Outcomes of ASTEC/EN.5 Lin Oncology Staff Meeting, 08.01.2009
  39. 39. ASTEC/EN.5 CONCLUSION <ul><li>Overall morbidity (which included documented postsurgical complications) was greater in the radiation therapy study arm (60% vs 26%). </li></ul><ul><li>No differences in recurrence-free, disease-specific, or overall survival (hazard ratio 1.01; P = 0.98) </li></ul><ul><li>Although it was not a primary end point of the study (not randomized to receive or not, vault brachytherapy) </li></ul><ul><ul><li>Decreased the risk of isolated recurrence in the vagina </li></ul></ul><ul><ul><li>(hazard ratio: 0.53; P = .038). </li></ul></ul><ul><ul><li>This reduction in local recurrence did not influence survival. </li></ul></ul>Lin Oncology Staff Meeting, 08.01.2009
  40. 40. ASTEC/EN.5 CONCLUSION (2) <ul><li>EBRT alone is not indicated in the treatment of women with early-stage endometrial cancer at intermediate risk of relapse </li></ul><ul><li>Further refinement of which subgroups of women might benefit from treatment would require an individual patient data meta-analysis. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  41. 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. 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
  43. 43. NSGO EC-9501/EORTC-55991 2008 Updated Results (1) <ul><li>Median follow-up: 4.3 years </li></ul><ul><li>Statistically significant improvement in progression-free survival (hazard ratio 0.62; P = .03) in favor of the combined modality. </li></ul><ul><li>Absolute difference in 5-year progression-free survival: 7% (79% vs. 72%). </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  44. 44. NSGO EC-9501/EORTC-55991 2008 Updated Results (2) <ul><li>Cancer-specific overall survival improved in radiation/ chemotherapy group (10% at 5 y. from 78 % to 88 % ). </li></ul><ul><li>Combined modality improved progression-free but also cancer specific overall survival </li></ul><ul><li>No difference of overall survival by randomization between combined modality and radiation alone </li></ul><ul><li>RT+CT was better than RT alone. </li></ul><ul><li>The next question is if RT+CT better than CT alone </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  45. 45. PORTEC – 2 (2008) <ul><li>Vaginal brachytherapy versus external beam pelvic radiotherapy for high-intermediate risk endometrial cancer: Results of the randomized PORTEC-2 trial </li></ul><ul><li>R. A. Nout, H. Putter, I. M. Joergenliemk-Schulz, J. J. Jobsen, L. C. Lutgens, E. M. van der Steen-Banasik, J. W. Mens, A. Slot, V. T. Smit and C. L. Creutzberg </li></ul><ul><li>Leiden University Medical Center, Leiden, Netherlands; University Medical Center Utrecht, Utrecht, Netherlands; Medisch Spectrum Twente, Enschede, Netherlands; MAASTricht Radiation Oncology Clinic, Maastricht, Netherlands; Radiotherapy Institute Arnhem, Arnhem, Netherlands; Daniel den Hoed Cancer Center, Rotterdam, Netherlands </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  46. 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
  47. 47. PORTEC – 2 Trial Results <ul><li>EBRT </li></ul><ul><li>Vaginal relapse: 1.9% </li></ul><ul><li>Locoreg. relapse: 2.5% </li></ul><ul><li>Distant relapse: 5.7% </li></ul><ul><li>Pelvic relapse: 0.6% </li></ul><ul><li>No deaths: 20 pts </li></ul><ul><li>DFS: 89% </li></ul><ul><li>OS: 90% </li></ul><ul><li>BT P </li></ul><ul><li> 0.9% (p = 0.97) </li></ul><ul><li> 4% (p = 0.15) </li></ul><ul><li>6.3% (p = 0.37) </li></ul><ul><li>3.5% (p = 0.03) </li></ul><ul><li>20 pts </li></ul><ul><li> 89% </li></ul><ul><li>90% </li></ul>Median F/U 36 months Lin Oncology Staff Meeting, 08.01.2009
  48. 48. PORTEC – 2 Toxicity Results <ul><li>EBRT </li></ul><ul><li>QOL Diarrhea ~30% </li></ul><ul><li>Impairment in: ~30% </li></ul><ul><li>daily activities </li></ul><ul><li>Decreased social: ~20% </li></ul><ul><li>functioning </li></ul><ul><li>G1-2 GI toxicity: 54% </li></ul><ul><li>G1-2 GU toxicity: 27% </li></ul><ul><li>Skin toxicity: 20% </li></ul>BT P ~10% (p = 0.001) ~13% (p = 0.03) ~10% (p=0.001) 13% (p = 0.001) 22% (p=0.1) 2% (p = 0.001) Lin Oncology Staff Meeting, 08.01.2009
  49. 49. PORTEC – 2 Conclusions <ul><li>VBT as effective as EBRT for intermediate high risk EC. </li></ul><ul><li>Despite the slightly but significantly increased pelvic failure rate in the VBT arm. </li></ul><ul><li>OS and RFS were similar. </li></ul><ul><li>QOL significantly better with brachytherapy </li></ul><ul><li>VBT should be the treatment of choice for patients with high-intermediate risk EC. </li></ul><ul><li>Remaining question: treat at recurrence or treat upfront? </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  50. 50. GOG # 99 vs PORTEC-2 <ul><li>GOG # 99 </li></ul><ul><li>(2004) </li></ul><ul><li>EBRT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a “high intermediate” risk definition. </li></ul><ul><li>PORTEC-2 </li></ul><ul><li>(2008) </li></ul><ul><li>Brachytherapy should be the treatment of choice for patients with high-intermediate risk endometrial carcinoma. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  51. 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
  52. 52. Trial design for JGOG 2033 Surgery >1/2 myometrial invasion, no residual tumor FIGO stage IC, IIA, IIB, IIIA, IIIB, IIIC RANDOMIZE Pelvic Radiation Therapy (PRT) Chemotherapy (CAP) Primary endpoint: Overall Survival Secondary endpoints: PFS, toxicity 475 pts. 238 pts. 237 pts. Enrollment: Jan 1994 - Dec 2000 TAH BSO+ PLN (95.3%) PRT:45-50Gy, PART (5.7%), Brachytherapy (3.1%) <ul><ul><li>Cyclophosphamide 333 mg/m2 </li></ul></ul><ul><ul><li>Doxorubicin 40 mg/m2 </li></ul></ul><ul><ul><li>Cisplatin 50 mg/m2 </li></ul></ul><ul><ul><li>Every 4 weeks for 3 or more courses </li></ul></ul>193 pts. 192 pts. Lin Oncology Staff Meeting, 08.01.2009
  53. 53. <ul><li>Comparison       PRT CAP </li></ul><ul><li>Completed Tx          98.9% 97.3% </li></ul><ul><li>Median No. of courses      -      3 ( 3-7 ) </li></ul><ul><li>Median duration of Tx        5.1 wks 11.4 wks </li></ul><ul><li>Stopped Tx due to toxicity    1.6% 4.8% </li></ul>Lin Oncology Staff Meeting, TREATMENT 08.01.2009
  54. 54. Adverse Effects <ul><li>Toxicity PRT (n=193) CAP (n=192) </li></ul><ul><li> </li></ul><ul><li>Grade 0-2 190 (98.4%) 181(95.3%) </li></ul><ul><li> 3-4 3 ( 1.6%) 9 (4.7%) </li></ul><ul><li>Tx-related death 0   (0%) 0   (0%) </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  55. 55. JGOG 2033 RESULTS Lin Oncology Staff Meeting, 08.01.2009
  56. 56. JGOG 2033 Conclusion <ul><li>Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer. </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  57. 57. <ul><li>ADVANCED ENDOMETRIAL CARCINOMA </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  58. 58. 422 PTS. 202 – WAI, 194 - PA Lin Oncology Staff Meeting, 08.01.2009
  59. 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%
  60. 60. Lin Oncology Staff Meeting, 08.01.2009
  61. 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. 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
  63. 63. <ul><li>P R O J E C T </li></ul><ul><li>RAMBAM HEALTH CARE CAMPUS </li></ul><ul><li>Oncology Division </li></ul><ul><li>Endometrial Cancer Adjuvant Treatment Policy </li></ul><ul><li>(Updated: November, 2008) </li></ul><ul><li>Z. Bernstein, A. Amit, E. Gez, S. Billan, R. Abdah-Bortnyak, </li></ul><ul><li>L. Lowenstein, A. Kuten </li></ul><ul><li>Based on the Guidelines of the Mallinckrodt Institute of Radiology </li></ul><ul><li>Washington University </li></ul><ul><li>(by Perry W. Grigsby, M.D.) </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  64. 64. Surgically staged patients at least 8 LN evaluated (4 from each side of the Pelvis) Lin Oncology Staff Meeting, 08.01.2009
  65. 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. 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. 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
  68. 68. SIGNIFICANT PELVIC RECURRENCE IN HIGH-RISK EC AFTER CT ALONE Staged according to the 1988 FIGO criteria (GOG #33) Lin Oncology Staff Meeting, <ul><li>1 43 high-risk endometrial cancer patients received adjuvant chemotherapy alone. </li></ul><ul><li>All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophor-ectomy. </li></ul><ul><li>All patients received 4–6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. </li></ul><ul><li>Most patients had Stage III–IV disease (83.7%) or unfavorable histology tumors (74.4%). </li></ul>08.01.2009
  69. 69. RESULTS (1) Lin Oncology Staff Meeting, Median follow-up was 27 months (range, 2–96 months). 08.01.2009
  70. 70. RESULTS (2) Lin Oncology Staff Meeting, 08.01.2009
  71. 71. Conclusions: <ul><li>PVR is common in high-risk pathologic Stage I–IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy </li></ul>Lin Oncology Staff Meeting, 08.01.2009
  72. 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. 73. THANK YOU ! 08.01.2009 Lin Oncology Staff Meeting,

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