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Ovarian cancer. 650-700 nye tilfælde årligt i DK (incl. 150-200 Borderline) Livstidsrisiko - 2% Udgør 30 % af alle gynækologiske cancere Udgør 3,8% af kræft hos kvinder Stiger med alderen 1/3 er yngre end 60 år 90 % epithelial carcinoma.

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ovarian cancer
Ovarian cancer
  • 650-700 nye tilfælde årligt i DK
  • (incl. 150-200 Borderline)
  • Livstidsrisiko - 2%
  • Udgør 30 % af alle
  • gynækologiske cancere
  • Udgør 3,8% af kræft hos kvinder
  • Stiger med alderen
  • 1/3 er yngre end 60 år
  • 90 % epithelial carcinoma
slide3

Årsager til kræft i æggestokken

  • Hypoteser
    • Celleskade ved ægløsningen
    • Påvirkning fra hormoner i kroppen
    • Udefra kommende carcinogener
etiology risk factors
EtiologyRisk factors
  • Hereditary – 10 %
    • BRCA I & II prof lap BSO
    • HNPCC
  • Reproductive factors
    • Nulliparity
    • Infertility
    • Contraceptive pill
    • Tidlig menarch – sen menopause
  • Exogene factors
    • Talcum
    • Tubal ligation / hysterectomi
slide5

Familiær mamma / ovarie cancer

  • HBOC
    • Kromosom 17q og 13q
    • BRCA1 og BRCA2
    • Defekt evne til at reparere DNA
slide6

Familiær kræft i tyktarm

  • HNPCC
    • Kromosom 2 og 7
    • Mismatch repair (MMR) system
        • hMLH1, hMSH2, hMSH6, and hPMS2
    • 45% risiko for kræft i livmoderen
    • 10 % risiko for kræft i æggestok
slide7

Symptomer ved kræft i æggestokken

  • er oftest svage....
          • Øget omfang af maven
          • Tyngdefornemmelse
          • Forstoppelse - diarré
          • Hyppig vandladning
          • Træthed
          • Almen sygdomsfølelse
slide8

STADIER

St IV

Yderligere spredning

St III

Også i øvre del

af bughulen

St.II

Begrænset til

underlivet

St. I

Begrænset til

æggestokkene

stage
Stage

St I only the ovary (ies)

St II pelvic involvement

St IIIa Upper abdomen microscopic

IIIb Upper abdomen < 2 cm

IIIc Upper abdomen > 2 cm or node pos.

St IV levermetastases, above diagphragm,

groins, bowel

slide10

Stadier

St IV - 70 %

Yderligere spredning

St III - 70%

Også i øvre del

af bughulen

St.II - 15 %

Begrænset til

underlivet

St. I - 15 %

Begrænset til

æggestokkene

slide11

Stadier

5-års overlevelse

St IV – 10-20 %

Yderligere spredning

St III - 40 %

Også i øvre del

af bughulen

St.II - 65 %

Begrænset til

underlivet

St. I - 85 %

Begrænset til

æggestokkene

prognosis 5 year suvival
Prognosis5 year suvival
  • St I 85%
  • St II 65%
  • St III 40 %

= 70 % of all o.c.

  • St IV 10-20 %
slide14

Udredning

        • Gynækologisk undersøgelse
        • Ultralydscanning
        • Blodprøver ~ CA-125
slide15

Udredning RMI(Risk of Malignancy Index)

  • Menopause x UL-score x CA-125
  • > 200 PAKKEFORLØB
c pet ct scanning diss sygdom
C PET-CT scanningdiss sygdom

hjertet

nyre

blæren

Herlev Hospital, klinisk fysiologisk afd.

slide18

Behandling

      • • Operation
      • • Kemoterapi
treatment ovarian cancer
Treatment – ovarian cancer
  • Surgery (RMI< 200: laparoscopy frozen section)
    • Bilat salpingooopherectomy
    • Hysterectomy
    • Omentectomy
    • Lymphadenectomy
    • (Appendectomy)

NO RECIDUAL TUMOR

Maximal debulking bowel, spleen, diagphragm

kemoterapi
Kemoterapi

To-tre-stof-behandling

Carboplatin og taxol, bevazicumab

6/3uger

slide21

Neoadjuverende kemoterapi - 3 serier

  • efterfulgt af operation
  • Dissimineret sygdom - inoperabel
  • Høj alder
  • Comorbiditet
teknik lille b kken
Teknik – lille bækken
  • Adgang til retroperitoneum
  • Ureteres frilægges
  • Uterus fjernes extraperitonealt,
  • idet vagina åbnes 3-9,

ned under peritoneum

sv.t fossa Douglasi,

så højt på rectum som nødvendigt

teknik vre abdomen
Teknik – øvre abdomen
  • Incisionen forlænges
  • Ligamentum falciforme deles
  • Leveren mobiliseres
  • Peritoneum på diagphragma reseceres skarpt
  • Omentectomi
  • Colonresektion, splenectomi, ect
slide25

Extensivt kirurgisk indgreb

omfattende

Lille bækken:

En bloc resektion af genitalia interna, peritoneum og tarmsegment, med primær tarmanastomose eller stomi, blære- og ureterresektion.

Øvre abdomen:

Omentectomi, operation på diaphragma (peritoneal resektion eller argon beaming), splenectomi, resektion cauda pancreatis, yderligere tarmresektion

Operationsvarighed 4-8 timer

slide26
Case
  • 39-årig kvinde
  • UL: bilat , multicyst ovarietumorer, hhv 6 og 4 cm
  • CA-125 = 63
  • Hvad gør vi ?
slide27

Udredning RMI(Risk of Malignancy Index)

  • Menopause x UL-score x CA-125
  • UL malignitetskriterier : > Bilokulær , Solide områder, Bilateral ,Excrescenser , Ascites, + Extra-ovariel sygdom
slide28

Udredning RMI(Risk of Malignancy Index)

  • Menopause x UL-score x CA-125
  • 1 x 3 x 63= 189 dvs < 200
slide29

Udredning RMI(Risk of Malignancy Index)

  • Menopause x UL-score x CA-125
  • < 200 Laparoskopi
  • USO til frys
slide30
Case
  • 46 årig præmenopausal kvinde
  • UL: multilokulær tumor, ve adnex
  • PET-CT: mulig carcinose i lille bækken + øvre abd
  • CA-125 = 841
  • Hvad gør vi ?
ben laparoskopi ved avanceret ovariecancer
Åben laparoskopi ved avanceret ovariecancer
  • Be-/afkræfte diagnosen – 2/3 vs 1/3
  • Vurdere operabilitet – 90 %,
  • Tilrettelægge/udnytte operationstid mere rationelt
  • Planlægge evt gastrokirurgisk assistence
  • Ingen neg effekt på prognosen
open laparoscopy in advanced ovarian cancer
Open laparoscopy in advanced ovarian cancer
  • Open laparoscopy - the best technique to
      • evaluate operability,
      • plan operating time of debulking surgery
      • make a histological diagnosis,
      • exclude other primary tumors (or benign disease)
      • refer patients to a tertiary center
other studies on laparoscopy to judge operability
Other studies on laparoscopy to judge operability
  • Fagotti et al (Gyn Oncol 2005): Optimal reduction in 90% of the patients jugded to be operable.
  • Deffieux et al (Int J Gyn Cancer 2006). 10/11 patients thought to be resectable were resected to no residual tumor.
  • Angioli et al (Gyn Oncol 2006): Optimal reduction (R0) in 96% of the patients jugded to be operable (i.e. n = 53/87 or 61%).
slide34
Open Laparoscopy in stage III and IV ovarian carcinoma (n=228,1995 - 2002)Vergote et al Int J Gynecol Cancer 2005 15:776-9
  • 55 patients (32%) with suspect ovarian mass in combination with omental cake and/or ascites have no ovarian carcinoma stage III or IV (metastases from other primaries, stage I-II, benign, ..)
  • 90% of the patients with advanced ovarian carcinoma (n = 173) judged to be operable were optimally debulked.
  • In 71 patients the port sites were completelyexcised at the time of debulking.
ben laparoskopi ved advanceret ovariecancer
Åben laparoskopi ved advanceret ovariecancer
  • Længdeincision (3 cm) under umbilicus
  • Fascie og peritoneum åbnes
  • Sikre sig fri adgang
  • Trokar med stump spids, ballon på peritonealsiden, skumkrave på hudsiden
laparoscopy to judge operability
Laparoscopy to judge operability

Definitions for inoperability:

  • Extended visceral peritoneal disease
  • Extended small bowel involvement
  • Large involvement of upper abdomen (diaphragm, liver, porta)
  • Heavily bleeding tumors

Sammenholdes med PET-CT

indications for neoadjuvant chemotherapy
Indications for neoadjuvant chemotherapy

1. Tumors larger than 2 cm around the superior mesenteric artery or around the porta hepatis, or

2. Intrahepatic (multiple) metastases or several extraabdominal metastases (excluding resectable inguinal or supraclavicular lymph nodes) larger than 2 cm , or

3. Poor general condition (e.g. > 80 years) making a “maximal surgical effort” to no residual tumor impossible, or

4. Extensive serosal invasion (e.g. plaques) of the intestines necesitating bowel resections of > 1.5 m

slide38
Case
  • C ovarii st IIIC, makroradikal operation 2012
  • Adjuv kemoterapi (carbo/tax)
  • 9 mdr kontrol: velbefindende
  • CA-125= 86

Hvad gør vi ?

slide39

Early treatment of relapsed ovarian cancer based on CA125 level alone versus delayed treatment based on conventional clinical indicators

Results of the randomized MRC OV05 and EORTC 55955 trials

Gordon Rustin (Mount Vernon Cancer Centre)

and Maria van der Burg

On behalf of all OV05 and 55955 Collaborators

31st May 2009

time from randomisation to second line chemotherapy

1.00

0.75

Proportion alive not started

second-line chemotherapy

0.50

0.25

0.00

0

3

6

9

12

15

18

21

24

Months since randomisation

Number at risk

Early

265

23

16

14

11

11

10

10

9

264

177

116

91

69

56

49

42

33

Delayed

Time from randomisation to second-line chemotherapy

Median (months)

Early 0.8

Delayed 5.6

HR=0.29 (95% CI 0.24, 0.35) p<0.00001

overall survival

1.00

0.75

Proportion surviving

0.50

0.25

0.00

0

6

12

18

24

30

36

42

48

54

60

Months since randomisation

Number at risk

Early

265

247

211

165

131

94

72

51

38

31

22

Delayed

264

236

203

167

129

103

69

53

38

31

19

Overall Survival

HR=1.00 (95%CI 0.82-1.22) p=0.98

Abs diff at 2 years= 0.1%

(95% CI diff= -6.8, 6.3%)

Early

Delayed

conclusions
Conclusions
  • In early treatment arm based on rise in CA125
    • Second-line chemotherapy started a median of 4.8 months earlier
    • Third-line chemotherapy started a median of 4.6 months earlier
  • This early treatment did not improve overall survival
      • HR=1.00, 95% CI 0.82-1.22, p=0.98
      • Absolute difference at 2 years 0.1% (95%CI -6.8, 6.3%)
  • Early chemotherapy does not improve Qol
slide43

HOT scientific topics

  • Ovarian cancer
  • Difference among countries
  • Lymphadenectomy
  • Extensive surgery
  • Neoadjuvant chemotharapy
  • Recurrence – surgery
slide44

HOT scientific topics

  • Ovarian cancer
  • Difference among countries
  • Lymphadenectomy
  • Extensive surgery
  • Neoadjuvant chemotharapy
  • Recurrence – surgery
benchmarking study
Benchmarking study
  • Modul 1: Basis-benchmarking på grundlag af eksisterende data
  • Modul 2: Patienters opmærksomhed på egen sundhedstilstand, herunder patienters kultur og opfattelser
  • Modul 3: Almen praksis’ kultur, opfattelser og ageren
  • Modul 4: Årsager til forsinkelser i diagnosticeringen
  • Modul 5: Behandlingskvalitet
slide46

Cancer survival in Australia, Canada, Denmark, Norway,Sweden, and the UK, 1995–2007 (the International CancerBenchmarking Partnership): an analysis of population-basedcancer registry data Lancet 2011; 377: 127–38

Interpretation Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival.

Data quality and changes in classification are not likely explanations.

The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older.

slide47

Stage at diagnosis and ovarian cancer survival: Evidence from the InternationalCancer Benchmarking Partnership, Gynecologic OncologyData from population-based cancer registries in Australia, Canada, Denmark, Norway, and the UK were analysed for 20,073 women diagnosed with ovarian cancer during 2004–07.

Results. One-year survival was 69% in the UK, 72% in Denmark and 74–75% elsewhere.

In Denmark, 74% of patients were diagnosed with FIGO stages III–IV disease, compared to 60–70% elsewhere.

International differences in survival were evident at each stage of disease; women in the UK had lower survival than in the other four countries for patients with FIGO stages III–IV disease (61.4% vs. 65.8–74.4%).

International differences were widest for older women and for those with advanced stage or with no stage data

slide50

HOT scientific topics

  • Ovarian cancer
  • Difference among countries
  • Lymphadenectomy
  • Extensive surgery
  • Neoadjuvant chemotharapy
  • Recurrence – surgery
lymphadenectomy prognostic impact
LymphadenectomyPrognostic impact
  • Correct staging – adjuvant therapy
  • Therapeutic impact - micrometastases
slide52

The potential therapeutic role of lymph node resection inepithelial ovarian cancer: a study of 13 918 patientsBritish Journal of Cancer (2007) 96, 1817–1822

For all patients, a more extensive lymph node dissection (0, 1, 2–5,

6–10, 11–20, >20 nodes) was associated with an improved 5-year disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8%, respectively (P<0.001)

Of the stage IIIC patients with nodal metastases, the extent of nodal resection (1, 2–5, 6–10, 11–20, >20 nodes) was associated with improved survivals of 36.9, 45.0, 47.8, 48.7, and 51.1%, respectively (P<0.023).

venter p det randomiserede studie
Venter på det randomiserede studie

du Bois

A multicenter, prospective randomised study of advanced ovarian cancer by the AGO Ovarian Cancer Study Group is planned to analyse the therapeutic impact of systematic lymphadenectomy in ovarian cancer

slide54

HOT scientific topics

  • Ovarian cancer
  • Difference among countries
  • Lymphadenectomy
  • Extensive surgery
  • Neoadjuvant chemotharapy
  • Recurrence – surgery
extensive surgery retrospektive studies
Extensive Surgery - Retrospektive studies

Aletti et al. Obstet Gynecol 2006;107:77-85

Chi et al Gyn Oncol 2006;103:559-564

Eisenhauer et al. Gyn Oncol 2006;103:1083-1090

Scholz et al. Gyn Oncol 2007;106:591-595.

Winter III WE et al. J Clin Oncol 2008;26:83-89

Conclusion: Increased PFS and OS among ptt with extensive surgery, with no residual tumor in selected patients with ovarian cancer stage IIIC

extensive surgery
Extensive Surgery

Randomised, phase III trial

+/- Maximal debulking

- behind the times

already a well established treatment

eortc 55971
EORTC 55971

Randomized Phase III study comparing upfront debulking surgery versus neo-adjuvant chemotherapy in patients with Stage IIIc or IV epithelial ovarian carcinoma.

CONCLUSION:

No difference in OS

slide60

HOT scientific topics

  • Ovarian cancer
  • Difference among countries
  • Lymphadenectomy
  • Extensive surgery
  • Neoadjuvant chemotharapy
  • Recurrence – surgery
slide61

Recurrence - surgery

Background

  • The primary treatment of ovarian cancer is surgery
  • 80-90 % have effect of adjuvant chemotherapyeffekt
  • (Carboplatin og Paclitaxel)
  • Neoadjuvant chemotherapy
  • Recurrence rate
  • 85%

DESKTOP v/ overlæge BJMosgaard

desktop studies
DESKTOP - studies

The Descriptive Evaluation of preoperative Selection KriTeria

for OPerability in recurrent OVARian cancer

objectives of the ago desktop series evaluating surgery in recurrent oc
Objectives of the AGO DESKTOP seriesevaluating surgery in recurrent OC

DESKTOP I: - descriptive analysis in a multi

AGO-OVAR OP.1 centre setting

- identify an appropriate endpoint

- creation of a model for a

predictive score for resectability

(allowing pts. selection for further studies)

DESKTOP II: - Validation of the predictive score

AGO-OVAR OP.2 - descriptive analysis of the selection

bias for offering surgery to ROC pts.

DESKTOP III: - Prospectively randomized trial to

AGO-OVAR OP.4 evaluate the impact on OS

slide64

AGO DESKTOP OVAR I

No residual tumor

median OS 45.2 mos.

Residual tumor > 10 mm

median OS 19.7 mos.

Recidual tumor 1 - 10 mm

median OS 19.6 mos.

DESKTOP OVAR I

Harter P, du Bois A, Hahmann M, et al. Ann Surg Oncol 2006

DESKTOP v/ overlæge BJMosgaard

ago score
AGO-score
  • Good performance status (ECOG 0)
  • No redidual tumor after primary surgery
  • No ascites at recurrence (< 500 ml)

AGO-score positivt (All three factors)

DESKTOP v/ overlæge BJMosgaard

ago desktop ovar i i
AGO DESKTOP OVAR II
  • Operation af kvinder med de gunstige egenskaber
  • (God almen tilstand, positiv primær kirurgi, væske i bughulen < 500ml)
  • KONKLUSION
  • AGO- score kan forudsige sandsynligheden for at man ved operationen for tilbagefald, kunne fjernet alt synligt kræftvæv hos 76%
  • Acceptabel komplikationsrate

DESKTOP v/ overlæge BJMosgaard

samlet konklusion ago desktop ovar i ii
SAMLET KONKLUSIONAGO DESKTOP OVAR I-II
  • Kun patienter med makroradikal operation havde gavn af kirurgi
  • AGO-scoren kan pålideligt selektere patienter med favorabelt kirurgisk resultat
  • Patienterne tålte operationen for tilbagefaldet lige så godt, som de tålte den primære operation ved udbredt sygdom

DESKTOP v/ overlæge BJMosgaard

slide68

AGO-OVAR OP.4

(AGO DESKTOP OVAR III)

Prospectively randomized evaluation of

cytoreductive surgery as adjunct preceding standardplatinum-based chemotherapy in platinum-sensitiverecurrent cancer of the ovary, fallopian tube, or peritoneum

AGO Study Group Ovarian Cancer (AGO-OVAR)

DESKTOP v/ overlæge BJMosgaard

slide69

DANSK GYNÆKOLOGISK CANCER

DGC

Dansk Selskab for Gynækologiog Obstetrik

Dansk Selskab for Onkologi

Dansk Selskab for Patologisk Anatomi og Cyt.

2005 12
2005-12
  • > 6000 patients
    • Ovarian cancer
    • Endometrial cancer
    • Cervical cancer
  • National based
    • LPR
    • CPR
    • Cancerregister