Beleid bij recidief/gemetastaseerd endometriumcarcinoom Philippe Van Trappen MD PhD Gynaecologisch/Oncologisch chirurg AZ Sint-Jan Brugge VVOG Jaarcongres 10-11/10/2013 Genk

Beleid bij recidief/gemetastaseerd endometriumcarcinoom Inhoud: Locatie recidief/metastasen endometrium carcinoom Beeldvorming bij diagnose van recidief/metastasen Chirurgie bij recidief endometrium carcinoom Chemotherapie bij recidief/gemetastaseerd endometrium carcinoom Moleculaire target therapieën

Locatie van recidief/gemetastaseerd endometriumcarcinoom . Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012

TABLE 1 Follow-up status of patients with endometrial cancer Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012. TABLE 1 Follow-up status of patients with endometrial cancer 2

Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012. TABLE 2 Clinical characteristics of all patients with endometrial cancer and patients who died of the disease FIGO IB (2009) 3

Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012. TABLE 3 Location of disease at the time of death for patients with endometrial cancer who died of the disease 4

Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012. FIGURE 1 . Location of disease at time of death for patients with endometrial cancer who died of the disease. 5

TABLE 4 Adjuvant treatment for patients who died of disease Location of Disease in Patients Who Die From Endometrial Cancer: A Study of 414 Patients From a Single Institution. Barlin, Joyce; Wysham, Weiya; Ferda, Aaron; Khoury-Collado, Fady; Cassella, Danielle; Alektiar, Kaled; Hensley, Martee; Chi, Dennis; Barakat, Richard; Abu-Rustum, Nadeem International Journal of Gynecological Cancer. 22(9):1527-1531, November 2012. TABLE 4 Adjuvant treatment for patients who died of disease 6

Endometriumcarcinoom patienten die overlijden aan hun ziekte: overlevingsduur na primaire diagnose? - Mediane ziekte-vrije overleving: 12.3 maanden (0.4-98.6 maanden) Mediane overleving: 20.5 maanden (0.4-116.4 maanden) 80% recidiveert binnen de eerste 24 maanden Type I endometriumcarcinoom (endometrioïde type): mediane overleving: 25.8 maanden Type II/high risk endometriumcarcinoom (UPSC, Clear cel ca): mediane overleving: 16.4 maanden

Identificeren van recidief/gemetastaseerd endometriumcarcinoom

PET-CT in identificeren locatie recidief/gemetastaseerd endometriumcarcinoom: SENSITIVITEIT

PET-CT in identificeren locatie recidief/gemetastaseerd endometriumcarcinoom: SPECIFICITEIT

PET-CT in follow-up bij symptomatische/asymptomatische patiënten met endometriumcarcinoom

Chirurgie recidief endometriumcarcinoom: bij wie? Locoregionaal recidief/letsel in voorheen bestraalde regio (evidentie: level C). Enkel indien maximale resectie mogelijk is, cfr meta-analyse 2010 (vroeger enkel exenteratie als type chirurgie). Rekening houden met co-morbiditeiten (cave: obesitas; cardiovasculair, etc.) Is patiente fit voor debulking chirurgie/exenteratie?

FIT FOR SURGERY?

14 retrospective studies (n patients: 20 to 75) 1997-2009 Total of 672 patients Optimal cytoreduction: 52% to 75% Complete surgical resection: 18% to 75%

Complete chirurgische resectie bij locaal gevorderd of recidief endometriumcarcinoom (GOG 122)

Beleid (palliatief) bij metastasen op afstand van een endometriumcarcinoom Progesteron receptor + of ? tumor Progestageen (bvb Megestrol acetaat*) Progesteron receptor - tumor Chemotherapie (paclitaxel/carboplatimum) (Evidentie: level C) * Fiorica JV et al, Gynecol Oncol, 2004 (GOG): Response Rate 27%, Median OS 14 maanden.

Chemotherapie voor recidiverend/gemetastaseerd endometrium carcinoom: mono- of combinatietherapie? Monotherapie Response Rate (RR) Cisplatinum 4-42% Carboplatinum 28-33% Doxorubicin 37% Epirubicin 26% 5-FU 41% Paclitaxel 36% Docetaxel 7.7-31% Gemcitabine 11% Grisham RN et al, Int J Gynecol Cancer, 2012 Nomura H et al, Ann Oncol, 2011 Katsumata N et al, Br J Cancer, 2005

Median Overall Survival Chemotherapie voor recidiverend/gemetastaseerd endometrium carcinoom: mono- of combinatietherapie? Combinatietherapie Response Rate (RR) Median Overall Survival (maanden) Cisplatinum+Docetaxel1 51.7% 21 Carboplatinum+Docetaxel1 48.3% 24 Carboplatinum+Paclitaxel1,2 60-67% 28 Carboplatinum+Paclitaxel+Epirubicin3 50% 26 Carboplatinum+Pegyl.Lip.Doxorubicin4 44% 21.4 Nomura H et al, Ann Oncol, 2011 Sorbe B et al, Int J Gynecol Cancer, 2008 Egawa-Takata T et al, Cancer Chem Pharm, 2011 du Bois A et al, Gynecol Oncol, 2007

Gemcitabine for Advanced Endometrial Cancer: A Retrospective Study of the Memorial Sloan-Kettering Cancer Center Experience. Grisham, Rachel; Adaniel, Christina; Hyman, David; Ma, Weining; Iasonos, Alexia; Aghajanian, Carol; Konner, Jason International Journal of Gynecological Cancer. 22(5):807-811, June 2012.

TABLE 3 Response by histology Gemcitabine for Advanced Endometrial Cancer: A Retrospective Study of the Memorial Sloan-Kettering Cancer Center Experience. Grisham, Rachel; Adaniel, Christina; Hyman, David; Ma, Weining; Iasonos, Alexia; Aghajanian, Carol; Konner, Jason International Journal of Gynecological Cancer. 22(5):807-811, June 2012. TABLE 3 Response by histology 4

2 verschillende casussen recidief endometriumcarcinoom 72jr Type 1 endom ca, FIGO IB, G3 Primaire behandeling: TAH-BSO + pelviene LND + adj ERT + IVBT RECIDIEF enkel thv vaginatop na 24 mnd: R/? Chirurgie + hormonale R/ 74jr Type 2 endom ca (UPSC, Prog R -), FIGO IIIC, G3 TAH-BSO + Pelv/Para-aort LND + omentum + biopten adj paclitaxel/carboplatinum RECIDIEF met intra-abdominale metastasen + vergrote para-aortische klieren (PET +) en + pleuravocht na 12 mnd Chemo (carboplatinum+paclitaxel) “almost 40% can be salvaged” (Rosenberg et al, 1993) “all patients who recurred from their UPSC died of their disease (Rosenberg et al, 1993)

Toekomst: moleculaire targets in endometrium carcinoom

Moleculaire target therapie in endometrium carcinoom

Moleculaire target therapie in endometrium carcinoom: Phase II trials