Uterine cancerAhmed Zeeneldin      Associate Prof of Medical Oncology      NCI      2010
Worldwide incidence and mortality                   Ahmed Zeeneldin   2
Ahmed Zeeneldin   3
—   US:    ◦ 40 000 new case/year    ◦ 8000 death/year— Incidence to mortality is 5:1— Sarcoma: 3% of uterine cancers     ...
NCI-Egypt            Ahmed Zeeneldin   5
Diagnosis and workup—   H&P    ◦ Postmenopausal vaginal bleeding—   CBCD, Biochemistry—   Chest x-ray—   Endometrial biops...
Endometrial pipette & biopsy                   Disposable, Flexible, 3 mm                   diameter                   Off...
Layers of the uterus                   Ahmed Zeeneldin   8
Uterine cancers                  Ahmed Zeeneldin   9
Staging of uterine CA    T1=FI         (T2=FII)      (T3=FIII)                (T4=FIVA)           N1= FIIIc        M1=FIVB...
TNM Staging 2010          Uterine carcinoma                                —   T1: Body                                   ...
TNM Staging 2010       Uterine sarcoma                                 —   T1: uterus                                     ...
Treatment of Pure endometrioid cancer         —   According to stage:             ◦ (1) disease limited to the corpus,    ...
Uterine sarcoma— Endometrial stromal sarcoma (ESS)— Leiomyosarcoma (LMS)— Undifferntiated sarcoma (UDS)                   ...
Treatment of uterine sarcoma                  Ahmed Zeeneldin   15
Adjuvant treatment of ESSHORMONE THERAPY(ESS only)  •Megestrol acetate  •Aromatase inhibitors (category 2B)  •Tamoxifen (c...
Adjuvant treatment of LMS, UDSChemotherapeutic agents (single or combinations)•Doxorubicin•Gemcitabine/docetaxel•Other sin...
Treatment of endometrial carcinoma                                Surg          RT                  ChemoLocal’zd   I     ...
HYSTERECTOMY—   TH/BSO: Total hysterectomy + bilateral salpingo-oophorectomy—   RH: Radical hysterectomy—   Pathologic ass...
Disease Limited to the Corpusstage I                    T1=FI                                                Confined to c...
Stage I          Ahmed Zeeneldin   21
Incompletely resected                  Ahmed Zeeneldin   22
Cervical Involvement (stage II)                                                 (T2=FII)—   If medically operable:        ...
Gross or suspected cervicalinvolvement (stage II)                     Ahmed Zeeneldin   24
Extra-uterine Disease: III-IV  —   Intra-abdominal : IIIA      (ascites, omental, nodal, ovarian, or               (T3=FII...
Stage III& IV                Ahmed Zeeneldin   26
Adjuvant Therapy—   Types:    ◦ RT: stage IC and above    ◦ Chemo: IC & G3—   Indications    ◦ Grade 3 (regardless of the ...
No adjuvant RT— IA G1-2 : observation— IB G1 : observation    ◦ (NB: IA G3: vag BT)    ◦ (NB: IB G3: vag BT)    ◦ (NB: IB ...
Adjuvant RT—   Uterine-confined disease:    ◦ RT:     – significantly decreased locoregional recurrence,       paticularli...
Adjuvant RT vs Chemo: GOG 122— Randall et al., J Clin Oncol. 2006 Jan  1;24(1):36-44.— Compared    ◦ Whole Abdominal RT (W...
Adjuvant RT vs Chemo                 Ahmed Zeeneldin   31
Adjuvant RT vs Chemo: PFS                 Ahmed Zeeneldin   32
Adjuvant RT vs Chemo: OS                 Ahmed Zeeneldin   33
AP vs AP+paclitaxel—   Homesley et al, Gynecol Oncol 2008;108:S2— GOG 184— AP+paclitaxel increased toxicity— No benefit   ...
Systemic therapy in endometrial ca—   Used in:    ◦ Recurrent    ◦ Metastatic or    ◦ High-risk disease—   Types:    ◦ Hor...
Chemotherapy in endometrial ca—   (Multi-agent chemotherapy regimens preferred, if    tolerated)    ◦   Cisplatin/doxorubi...
Relapse— Isolated locaoregional recurrence— Solitary metastasis— Disseminated metastases                         Ahmed Zee...
Isolated locoregional recurrence—   No prior RT to the site:    ◦ RT or    ◦ Surgery then RT +/- chemo—   Prior RT to the ...
Disseminated metastases—   Asymptomatic or low grade (G1):    ◦ Hormonal therapy à progression à chemo      à progression ...
Solitary metastasis— Resectable:— Surgery +/- RT à progression (as  disseminated)— Irresectable: as disseminated          ...
Hormone Replacement Therapy forEndometrial Cancers— Follows TH or RH/BSO— Early menopasue:    ◦   hot flashes,    ◦   mood...
Hormone Replacement Therapy forEndometrial Cancers—   Controversial    ◦ Beneficial or detrimental to uterine CA:     – In...
Progestens as alternative to surgery—   Indications:    ◦ young women who desire fertility preservation      with either  ...
Treatment of Relapsed or MetastaticDisease— Surgery: surgery and or RT— RT: suregry, re-RT, hormonal therapy, CTh         ...
Hormonal Therapy in metastaticuterine ca—   Indications:    ◦ Endometrioid histologies only    ◦ Asymptiomatic—   contrain...
Progestins in Met Uterine ca— Thigpen et al, J Clin Oncol  1999;17(6):1736-1744.— RCT between PO:— MPA: LD 200 mg/d— MPA: ...
Progestins in Met Uterine ca                   Ahmed Zeeneldin   47
Progestins in Met Uterine ca                   Ahmed Zeeneldin   48
Progestins in Met Uterine ca                   Ahmed Zeeneldin   49
Progestins in Met Uterine ca                   Ahmed Zeeneldin   50
Arzoxifene (SERM)in met uterine ca— Burkeet al, Gynecol Oncol 2003;90(2 Pt  2):S40-46.— RR 28%                        Ahme...
Tamoxifen in met uterine ca: GOGstudy—   Thigpen et al, J Clin Oncol 2001;19(2):364-367.— RR 10% (CR 4%)— PFS: 1.9 m— OS: ...
Chemotherapy for Metastatic andRecurrent Disease—   Indications:    ◦   Symptomatic,    ◦   Grade 2-3, or    ◦   large-vol...
Cis-doxo +/- pacli: RCT—   GOG: Fleming et al, J Clin Oncol. 2004 Jun 1;22(11):2159-66.— Cis 50, doxo 60 (45) mg/sm D1 q3w...
Pacli-carbo:—   1. Sovak et al, Int J Gynecol Cancer. 2007 Jan-Feb;17(1):197-203.—   2. Pectasides D et al, Gynecol Oncol....
Aggressive uterine epithelial CAs—   Include:    ◦ Papillary Serous Carcinomas,    ◦ Clear Cell Carcinomas, and    ◦ Carci...
Aggressive uterine epithelial CAs—   Surgery:    ◦ TAH/BSAO+ Pelvic & PA LND + staging—   Adjuvant:    ◦ Stage IA:      – ...
Ahmed Zeeneldin   58
Chemotherapy—   Papillary Serous Carcinomas, Clear Cell    Carcinomas:    ◦ Ovarian like: paltinum-taxane—   Carcinosarcom...
Carcinosarcoma, Adjuvant—   Sutton et al, Gynecol Oncol. 2005 Mar;96(3):630-4.    ◦ Ifo 1.5 gm/sm D1-5 vs    ◦ Ifo 1.6gm/s...
Metastatic carcinosarcoma—   Homesley et al, J Clin Oncol. 2007 Feb 10;25(5):526-31.    ◦ Ifo 2 gm/sm D1-3 vs    ◦ Ifo 1.6...
Metastatic carcinosarcomaREVIEW—   Powell et al, J Clin Oncol. 2010 ;28(5):2727-2731.    ◦ Ifo 1.6gm/sm D1-3+ pali 135 mg/...
Uterine Sarcomas—   Endometrial stromal sarcoma (ESS): low grade—   Undifferentiated sarcoma (high-grade undifferentiated ...
Treatment—   If medically operable:    ◦ Surgery: TH/BSO +/- LND—   If medically inoperable:    ◦ 1) pelvic RT (with or wi...
Low-Grade ESS(adjuvant treatment)—   If medically operable:    ◦ Surgery: TH/BSO +/- LND    ◦ Adjuvant:     – Stage I and ...
Leiomyosarcoma and High-GradeUndifferentiated Sarcoma—   Non-metastatic disease:    ◦ Surgery: TH/BSO +/- LND    ◦ Adjuvan...
SYSTEMIC THERAPYFOR UTERINE SARCOMA—   CHEMOTHERAPYREGIMENS    ◦   single agents or in combination, as clinically appropri...
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Uterine cancer 10 2011

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This is a comprehensive overview of Uterine carcinoma: diagnosis, staging and treatment

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Uterine cancer 10 2011

  1. 1. Uterine cancerAhmed Zeeneldin Associate Prof of Medical Oncology NCI 2010
  2. 2. Worldwide incidence and mortality Ahmed Zeeneldin 2
  3. 3. Ahmed Zeeneldin 3
  4. 4. — US: ◦ 40 000 new case/year ◦ 8000 death/year— Incidence to mortality is 5:1— Sarcoma: 3% of uterine cancers Ahmed Zeeneldin 4
  5. 5. NCI-Egypt Ahmed Zeeneldin 5
  6. 6. Diagnosis and workup— H&P ◦ Postmenopausal vaginal bleeding— CBCD, Biochemistry— Chest x-ray— Endometrial biopsy: ◦ Epithelial carcinoma ◦ Stromal / mesenchymal tumors— Suspected cervix involvement: ◦ Cervical Bx or MRI— CT or MRI: ◦ to show abdominal or pelvic extension Ahmed Zeeneldin 6
  7. 7. Endometrial pipette & biopsy Disposable, Flexible, 3 mm diameter Office procedure, no anaesthesia False negatives (FN): 10% FN in symptomatic: F D&C hystroscopy Ahmed Zeeneldin 7
  8. 8. Layers of the uterus Ahmed Zeeneldin 8
  9. 9. Uterine cancers Ahmed Zeeneldin 9
  10. 10. Staging of uterine CA T1=FI (T2=FII) (T3=FIII) (T4=FIVA) N1= FIIIc M1=FIVBConfined to Cervix Outside Uterus Bladder or bowel N1: pelvic Distantcorpus stroma* but A: Serosa, adenxa, cancer mucosa (3c1) Mets not Outside cells in ascites or N2: ParaaorticA: endometrium uterus peritoneal washings (3c2)or myometrium B: Vagina/parametrium+inner halfB: myometriumouter half Endocervical involvement is not considered T2 Grade is important: G1: well, G2: moderate, G3: poorly differentiated Ahmed Zeeneldin 10
  11. 11. TNM Staging 2010 Uterine carcinoma — T1: Body ◦ T1a: endometrium OR ◦ myometrium inner half ◦ T1b: myometrium outer half — T2: cervical stroma — T3: outside uterus ◦ T3a: Serosa, adenxa, malignant ascites ◦ T3b: parametrium /vagina — T4: bladder or bowel mucosa T1 T2 T3 T4 M1 — N1: regional LN+N0 I II III IVA IVB ◦ N1: pelvicN+ IIIC IIIC IIIC IIIC IVB ◦ N2 ParaaorticSIMPLIFICATION (FIGO stage) — M1: Distant mets-I: T1 -II:T2-III:T3 OR LN+ -IV:T4 OR M1
  12. 12. TNM Staging 2010 Uterine sarcoma — T1: uterus ◦ T1a: <= 5 cm ◦ T1b: > 5 cm — T2: invade pelvic tissues ◦ T2a: adenexa ◦ T2b: other pelvic tisues — T3: invade abdominal tissues ◦ T3a: One site ◦ T3b: multiple sites T1 T2 T3 T4 M1 — T4: bladder or bowel mucosa N0 I II III IVA IVB — N1: regional LN+ N+ IIIC IIIC IIIC IIIC IVB — M1: Distant metsSIMPLIFICATION (FIGO stage)-I: T1 -II:T2-III:T3 OR LN+ -IV:T4 OR M1
  13. 13. Treatment of Pure endometrioid cancer — According to stage: ◦ (1) disease limited to the corpus, ◦ (2) suspected or gross cervical involvement, (3) suspected extra-uterine disease. T1=FI (T2=FII) (T3=FIII) (T4=FIV) Confined to corpus Cervix but not Serosa, adenxa, cancer Bladder or bowel Outside uterus cells in ascites or mucosa endometrium (T1a=IA) Endocervix (T2a=FIIA) peritoneal washings Extrapelvicmyometrium inner half (T1b=IB) Cervical stroma (T3a=FIIIA) extension (T4=FIVA)myometrium outer half (T1c=IC) (T2b=FIIB) Vagina (T3b=FIIIB) LN: pelvic or paraaortic Distant mets = IVB (N1=FIIIB) Ahmed Zeeneldin 13
  14. 14. Uterine sarcoma— Endometrial stromal sarcoma (ESS)— Leiomyosarcoma (LMS)— Undifferntiated sarcoma (UDS) Ahmed Zeeneldin 14
  15. 15. Treatment of uterine sarcoma Ahmed Zeeneldin 15
  16. 16. Adjuvant treatment of ESSHORMONE THERAPY(ESS only) •Megestrol acetate •Aromatase inhibitors (category 2B) •Tamoxifen (category 2B) •Medroxyprogesterone acetate •GnRH analogs (category 2B) Ahmed Zeeneldin 16
  17. 17. Adjuvant treatment of LMS, UDSChemotherapeutic agents (single or combinations)•Doxorubicin•Gemcitabine/docetaxel•Other single agent options (category 2B): Dacarbazine, paclitaxel•gemcitabine, ifosfamide, docetaxel, epirubicin, liposomaldoxorubicin Ahmed Zeeneldin 17
  18. 18. Treatment of endometrial carcinoma Surg RT ChemoLocal’zd I uterus Yes* Adj RT may Adj CT may (G3 or IB/C) (G3 + IC/IB) II cervix Yes * adjRT in all Adj CT in G3 ORà RT then Surgextraut IIIA abdomen Yes adj RT Adj CT in G3 IIIB Pelvis May after RT RT may IVA vag/param /bladd/rectmmets IVB mets yes May Palliative CT OR hormonal T * If surgery is not feasible à RT Ahmed Zeeneldin 18
  19. 19. HYSTERECTOMY— TH/BSO: Total hysterectomy + bilateral salpingo-oophorectomy— RH: Radical hysterectomy— Pathologic assessment to include: ◦ Nodes – Level of nodal involvement (pelvic, common iliac, para-aortic) ◦ Peritoneal cytology ◦ Uterus – Ratio of depth of myometrial/stromal invasion to myometrial thickness – Cervical stromal or glandular involvement – Tumor size – Tumor location (fundus vs lower uterine segment/cervix) – Histologic subtype with grade – Lymphovascular space invasion – Consider mismatch repair analysis to identify genetic problems ◦ Fallopian tubes/ovaries Ahmed Zeeneldin 19
  20. 20. Disease Limited to the Corpusstage I T1=FI Confined to corpus— If medically operable: endometrium (T1a=IA) ◦ Surgery myometrium inner half (T1b=IB) myometrium outer half (T1c=IC) – TH/BSO + Pelvic & PA LND – inspection and palpation of diaphragm, liver, omentum, and pelvic and bowel peritoneal surfaces)— If medically inoperable: ◦ RT— Adjuvant: ◦ RT for high grade ◦ +Chemo for IC/IB G3 Ahmed Zeeneldin 20
  21. 21. Stage I Ahmed Zeeneldin 21
  22. 22. Incompletely resected Ahmed Zeeneldin 22
  23. 23. Cervical Involvement (stage II) (T2=FII)— If medically operable: Cervix but not Outside ◦ Surgery: RH/BSO + Pelvic&PA LND uterus •Endocervix (T2a=FIIA) OR •Cervical stroma (T2b=FIIB) ◦ RT --> surgery (TH/BSO + PA LND)— If medically inoperable: ◦ RT— Adjuvant: ◦ RT in stage II ◦ +Chemo for G3 Ahmed Zeeneldin 23
  24. 24. Gross or suspected cervicalinvolvement (stage II) Ahmed Zeeneldin 24
  25. 25. Extra-uterine Disease: III-IV — Intra-abdominal : IIIA (ascites, omental, nodal, ovarian, or (T3=FIII) peritoneal involvement): ◦ Surgery: TH/BSO + Pelvic and PA LND + Serosa, adenxa, cancer maximum debulking cells in ascites or peritoneal washings ◦ Adjuvant: (T3a=FIIIA) – RT Vagina (T3b=FIIIB) – +chemo for G3 LN: pelvic or paraaortic (N1=FIIIB) — Extrauterine pelvic : IIIB-IVA (vaginal, bladder, bowel/rectal, or parametrial involvement): (T4=FIV) ◦ RT and brachytherapy +/- surgery and Bladder or bowel mucosa chemotherapy. Extrapelvic extension — Distant mets: IVB (liver, lung) (T4=FIVA) ◦ TH/BSO +/- RT, hormonal therapy, or Distant mets = IVB chemotherapy Ahmed Zeeneldin 25
  26. 26. Stage III& IV Ahmed Zeeneldin 26
  27. 27. Adjuvant Therapy— Types: ◦ RT: stage IC and above ◦ Chemo: IC & G3— Indications ◦ Grade 3 (regardless of the stage): RT + Chemo ◦ Deeper invasion; > ½ of myometrium (regardless of grade) stage IC: RT ◦ LN+, stage IIIB: chemo or RT ◦ Others: – Age – LVI – Tumor volume – Involvement of lower uterine segment: Ahmed Zeeneldin 27
  28. 28. No adjuvant RT— IA G1-2 : observation— IB G1 : observation ◦ (NB: IA G3: vag BT) ◦ (NB: IB G3: vag BT) ◦ (NB: IB G2: observation or vag BT Ahmed Zeeneldin 28
  29. 29. Adjuvant RT— Uterine-confined disease: ◦ RT: – significantly decreased locoregional recurrence, paticularliy in the vagina – it did not increase OS or decrease mets – Type: EB vs Brachytherapy – whole pelvic RT & vag brachytherapy are equally effective – Vag brachyteherapy is less toxic— Extrauterine disease:— Adjuvant therapy Ahmed Zeeneldin 29
  30. 30. Adjuvant RT vs Chemo: GOG 122— Randall et al., J Clin Oncol. 2006 Jan 1;24(1):36-44.— Compared ◦ Whole Abdominal RT (WAI) & ◦ Chemo AP: doxorubicin A, Cisplatin P – 7 cycles: D 60mg/sm, P 50 mg/sm q 3w – 8th: only P— Stage III and IV Ahmed Zeeneldin 30
  31. 31. Adjuvant RT vs Chemo Ahmed Zeeneldin 31
  32. 32. Adjuvant RT vs Chemo: PFS Ahmed Zeeneldin 32
  33. 33. Adjuvant RT vs Chemo: OS Ahmed Zeeneldin 33
  34. 34. AP vs AP+paclitaxel— Homesley et al, Gynecol Oncol 2008;108:S2— GOG 184— AP+paclitaxel increased toxicity— No benefit Ahmed Zeeneldin 34
  35. 35. Systemic therapy in endometrial ca— Used in: ◦ Recurrent ◦ Metastatic or ◦ High-risk disease— Types: ◦ Hormonal: endometroid histology only – Aromatase inhibitors – Progestational agents – tamoxifen ◦ Chemo Ahmed Zeeneldin 35
  36. 36. Chemotherapy in endometrial ca— (Multi-agent chemotherapy regimens preferred, if tolerated) ◦ Cisplatin/doxorubicin (category 1 adjuvant) ◦ Cisplatin/doxorubicin/paclitaxel(category 1 metastatic) ◦ Ifosfamide plus paclitaxel(category1for carcinosarcoma) ◦ Carboplatin ◦ Carboplatin/paclitaxel ◦ Cisplatin ◦ Doxorubicin ◦ Paclitaxel ◦ Cisplatin/ifosfamide(forc arcinosarcoma) ◦ Ifosfamide (forcarcinosarcoma) Ahmed Zeeneldin 36
  37. 37. Relapse— Isolated locaoregional recurrence— Solitary metastasis— Disseminated metastases Ahmed Zeeneldin 37
  38. 38. Isolated locoregional recurrence— No prior RT to the site: ◦ RT or ◦ Surgery then RT +/- chemo— Prior RT to the site: ◦ Surgery +/- RT +/- chemo or ◦ Hormonal therapy or ◦ chemotherapy Ahmed Zeeneldin 38
  39. 39. Disseminated metastases— Asymptomatic or low grade (G1): ◦ Hormonal therapy à progression à chemo à progression àBSC— Symptomatic or high grade (G2,3) or large volume: ◦ Chemo and or RT à progression àBSC Ahmed Zeeneldin 39
  40. 40. Solitary metastasis— Resectable:— Surgery +/- RT à progression (as disseminated)— Irresectable: as disseminated Ahmed Zeeneldin 40
  41. 41. Hormone Replacement Therapy forEndometrial Cancers— Follows TH or RH/BSO— Early menopasue: ◦ hot flashes, ◦ mood lability, ◦ Vaginal dryness, ◦ pelvic soft tissue atrophy, ◦ osteoporosis, and ◦ an increased risk of cardiovascular disease. Ahmed Zeeneldin 41
  42. 42. Hormone Replacement Therapy forEndometrial Cancers— Controversial ◦ Beneficial or detrimental to uterine CA: – In normal women: + endometrial ca – In endometrial ca: no + in relapse ◦ + breast cancer— Can be used individualy in low risk patients— 6-12 months after adjuvant therapy— Raloxifene can be used Ahmed Zeeneldin 42
  43. 43. Progestens as alternative to surgery— Indications: ◦ young women who desire fertility preservation with either – atypical endometrial hyperplasia or – grade 1 endometrial hyperplasia; or ◦ women who are very poor surgical candidates.— Agents: ◦ medroxyprogesterone acetate (MPA 200mg/d PO) or ◦ Megestrol acetate— How: ◦ Progestins plus repeated D&C Ahmed Zeeneldin 43
  44. 44. Treatment of Relapsed or MetastaticDisease— Surgery: surgery and or RT— RT: suregry, re-RT, hormonal therapy, CTh Ahmed Zeeneldin 44
  45. 45. Hormonal Therapy in metastaticuterine ca— Indications: ◦ Endometrioid histologies only ◦ Asymptiomatic— contraindications: ◦ papillary serous, clear cell, or carcinosarcoma— Agents: ◦ Progestational agents: Mainly MPA 200mg/d PO ◦ Tamoxifen and aromatase inhibitors can be used— Predictors of response: ◦ well-differentiated tumors, ◦ a long disease-free interval, and ◦ the location and extent of extrapelvic (particularly pulmonary) metastases. Ahmed Zeeneldin 45
  46. 46. Progestins in Met Uterine ca— Thigpen et al, J Clin Oncol 1999;17(6):1736-1744.— RCT between PO:— MPA: LD 200 mg/d— MPA: HD 1000 mg/d Ahmed Zeeneldin 46
  47. 47. Progestins in Met Uterine ca Ahmed Zeeneldin 47
  48. 48. Progestins in Met Uterine ca Ahmed Zeeneldin 48
  49. 49. Progestins in Met Uterine ca Ahmed Zeeneldin 49
  50. 50. Progestins in Met Uterine ca Ahmed Zeeneldin 50
  51. 51. Arzoxifene (SERM)in met uterine ca— Burkeet al, Gynecol Oncol 2003;90(2 Pt 2):S40-46.— RR 28% Ahmed Zeeneldin 51
  52. 52. Tamoxifen in met uterine ca: GOGstudy— Thigpen et al, J Clin Oncol 2001;19(2):364-367.— RR 10% (CR 4%)— PFS: 1.9 m— OS: 8.8 m— Conclusion: Not to be used Ahmed Zeeneldin 52
  53. 53. Chemotherapy for Metastatic andRecurrent Disease— Indications: ◦ Symptomatic, ◦ Grade 2-3, or ◦ large-volume disseminated metastases ◦ Failure of hormonal therapy— Single-agent: RR 20-35%— Cisplatin, carboplatin, paclitaxel, and doxorubicin. Ahmed Zeeneldin 53
  54. 54. Cis-doxo +/- pacli: RCT— GOG: Fleming et al, J Clin Oncol. 2004 Jun 1;22(11):2159-66.— Cis 50, doxo 60 (45) mg/sm D1 q3w— Cis 50, doxo 45 D1, pacli 160 mg/sm D2 +GCSF q3w Cis-doxo Cis-doxo-pacli N 135 135 RR 34 57% (S) PFS 5m 8 m (S) OS 12 m 15 m (S) G2-3 Neurotxicity 5 39% Ahmed Zeeneldin 54
  55. 55. Pacli-carbo:— 1. Sovak et al, Int J Gynecol Cancer. 2007 Jan-Feb;17(1):197-203.— 2. Pectasides D et al, Gynecol Oncol. 2008 May;109(2):250-4. Sovak Pectasides N 85 47 Failed 1st line De no vo, or failed RR (CR) 43 (5)% 62 (21)% PFS 5.3m 15 m OS 13.2 m 25 m Ahmed Zeeneldin 55
  56. 56. Aggressive uterine epithelial CAs— Include: ◦ Papillary Serous Carcinomas, ◦ Clear Cell Carcinomas, and ◦ Carcinosarcomas (MMTs)— Characters: ◦ All are high grade (g3) and aggressive ◦ Mimic ovarian Ca— Treatment as Ovarian ca ◦ TAH/BSAO+Pelvic & PA LND + staging ◦ Adjuvant: individiulaized Ahmed Zeeneldin 56
  57. 57. Aggressive uterine epithelial CAs— Surgery: ◦ TAH/BSAO+ Pelvic & PA LND + staging— Adjuvant: ◦ Stage IA: – Observation – chemotherapy, or – Tumor-directed RT. ◦ Stage IB-II (also adequately debulked III and IV) – Chemotherapy +/- tumor-directed RT, or – Whole abdominopelvic RT +/- vaginal brachytherapy ◦ Inadequately debulked atage III and IV: – Chemotherapy Ahmed Zeeneldin 57
  58. 58. Ahmed Zeeneldin 58
  59. 59. Chemotherapy— Papillary Serous Carcinomas, Clear Cell Carcinomas: ◦ Ovarian like: paltinum-taxane— Carcinosarcomas (MMTs): ◦ Ifosfamide is the most active ◦ Ifosfamide-paclitaxel (category A) ◦ Ifosfamide-cisplatin ◦ Carboplatin-paclitaxel is also active Ahmed Zeeneldin 59
  60. 60. Carcinosarcoma, Adjuvant— Sutton et al, Gynecol Oncol. 2005 Mar;96(3):630-4. ◦ Ifo 1.5 gm/sm D1-5 vs ◦ Ifo 1.6gm/sm D1-5+ cispaltin 20 mg/sm D1-5— Stage I, II Ifofamide- cisplatin 65 2y- and 8y-PFS 69, 54% 2y- , 5y- and 8-y OS 82, 62, 52% Ahmed Zeeneldin 60
  61. 61. Metastatic carcinosarcoma— Homesley et al, J Clin Oncol. 2007 Feb 10;25(5):526-31. ◦ Ifo 2 gm/sm D1-3 vs ◦ Ifo 1.6gm/sm D1-3+ pali 135 mg/sm D1+ GCSF— Stage III, IV and recurrent Ifoffamide Ifoffamide- paclitaxel 91 88 RR 29 45% PFS 3.6 5.8 m (S) OS 8.4 13.5 m (S) Neuropathy 8 30% Ahmed Zeeneldin 61
  62. 62. Metastatic carcinosarcomaREVIEW— Powell et al, J Clin Oncol. 2010 ;28(5):2727-2731. ◦ Ifo 1.6gm/sm D1-3+ pali 135 mg/sm D1+ GCSF— Stage III, IV and recurrent Ifoffamide - Ifoffamide- paclitaxel cisplatin RR PFS OS toxicity More Less Ahmed Zeeneldin 62
  63. 63. Uterine Sarcomas— Endometrial stromal sarcoma (ESS): low grade— Undifferentiated sarcoma (high-grade undifferentiated sarcoma (HGUD) or Pure heterologous sarcoma— Leiomyosarcoma (LMS) Ahmed Zeeneldin 63
  64. 64. Treatment— If medically operable: ◦ Surgery: TH/BSO +/- LND— If medically inoperable: ◦ 1) pelvic RT (with or without brachytherapy) and chemotherapy; ◦ 2) chemotherapy; or ◦ 3) hormone therapy (but only for low-grade ESS). Ahmed Zeeneldin 64
  65. 65. Low-Grade ESS(adjuvant treatment)— If medically operable: ◦ Surgery: TH/BSO +/- LND ◦ Adjuvant: – Stage I and II: – Observation – Stage III and IV: – Hormonal therapy: – Megestrol acetate, medroxyprogesterone, – Tamoxifen, GnRH analogs, AI – RT may be added (decrease recurrences but no OS advantage)— Inoperable or Recurrent – Hormonal therapy: Ahmed Zeeneldin 65
  66. 66. Leiomyosarcoma and High-GradeUndifferentiated Sarcoma— Non-metastatic disease: ◦ Surgery: TH/BSO +/- LND ◦ Adjuvant: – RT controversial and individualized – Cth: may be considered due to high risk of systemic relapse – Stage I and II completely resected: – Observe – RT +/- brachtherapy – Cth: doxorubicin— Metastatic /advanced disease: – Single-agent dacarbazine, docetaxel, liposomal doxorubicin, epirubicin, gemcitabine, ifosfamide, and paclitaxel Ahmed Zeeneldin 66
  67. 67. SYSTEMIC THERAPYFOR UTERINE SARCOMA— CHEMOTHERAPYREGIMENS ◦ single agents or in combination, as clinically appropriate: ◦ Doxorubicin (most active single agent for LMS) ◦ Gemcitabine/docetaxel ◦ Single-agent dacarbazine, docetaxel, epirubicin, gemcitabine, ifosfamide, liposomal doxorubicin paclitaxel , TEMPZOLAMIDE and could also be considered (category 2B)— HORMONE THERAPY(Low-grade ESS only) ◦ Megestrol acetate ◦ Aromatase inhibitors (category 2B) ◦ Tamoxifen (category 2B) ◦ Medroxyprogesterone acetate ◦ GnRH analogs (category 2B) Ahmed Zeeneldin 67
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