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    1. 5. International Gynecologic Cancer Society Founded in 1986 Multidisciplinary Over 1500 members in more than 80 countries
    2. 6. IGCS Mission <ul><li>To promote the health and well-being of women with gynaecological cancer across the world </li></ul><ul><li>To improve research into prevention, and early detection, treatment and quality of life of women with gynaecological cancers </li></ul><ul><li>To promote the highest standard of professional care of women with gynaecological malignancies </li></ul>
    3. 7. IGCS Initiatives <ul><li>Publishes International Journal of Gynecological Cancer with ESGO </li></ul><ul><li>Meets every two years , rotating among Americas, Asia/Australia/Oceania and Europe/Africa/Middle East with reduced registrations rates for trainees, nurses and persons from less developed countries (Bangkok 2008: only 150$) </li></ul>
    4. 8. IGCS Initiatives (1) <ul><li>IGCS Workshop program for Lower-income countries with financial support for up to 10 meetings in 2008. </li></ul><ul><li>Travelling Scholarships in 2007-8: 20 of 5000-10000 $ (Current deadline October 31st). </li></ul><ul><li>Partner in Global Initiative on Women’s Cancer (GLOW) </li></ul>
    5. 9. IGCS Initiatives (2) <ul><li>www.IGCS.ORG </li></ul><ul><li>Website based tumor boards with expert opinions and voting system. </li></ul><ul><li>On line Journal Clubs with commentaries on controversial topics or papers. </li></ul><ul><li>Off year meetings in other continents than the Biennial meetings: eg Brazil April 2008 </li></ul>
    6. 10. IGCS <ul><li>Website: www.igcs.org </li></ul><ul><li>Email: [email_address] </li></ul><ul><li>Membership rates based on World Bank country income levels </li></ul>
    7. 12. IGCS Workshop “ Gynecologic malignancies” 8-9 September, 2008, Ankara, Turkey Vesna Kesic Instiute of Obstetrics and Gynecology Clinical Center of Serbia Cancer and Pregnancy
    8. 13. <ul><li>Biological uniqueness of cancer </li></ul><ul><li>in pregnancy is the combination of </li></ul><ul><li>an uncontrolled growth of a malignant tumour </li></ul><ul><li>a controlled growth of a feto-placental complex </li></ul><ul><li>inside the same body. </li></ul>
    9. 14. The biggest physiological process of human reproduction and the biggest pathological process which in most cases results in death are linked in the battle fought between immortality and destruction
    10. 15. The occurrence of cancer in pregnancy is relatively rare, about 1 case per 1000 deliveries
    11. 16. Cancer in pregnancy- the cruelest dillema Does the women lose the baby to save her life or risk her life to try to save baby ?
    12. 17. Is the potential life of an unborn child more important than prolonging a life of a young woman? Whose life is of greater value? And whose decision is this anyway ? ?
    13. 18. Fetus Mother Pregnancy Risk
    14. 19. For women diagnosed with cancer waiting for 40 weeks could be a death sentence particularly with high-grade, aggressive or metastatic cancers .
    15. 20. Malignant disease in pregnancy complicates the management of both cancer and the pregnancy.
    16. 21. The diagnostic and therapeutic approach is particularly difficult because it involves two persons: the mother and the baby .
    17. 22. Obstetricians and Oncologists should offer at the same time optimal : - maternal treatment - fetal well-being
    18. 23. Treatment that may be essential for the mother may be fatal or highly damaging for the baby.
    19. 24. <ul><li>Factors influencing the management </li></ul><ul><li>of pregnant women diagnosed with cancer </li></ul><ul><li>Stage of cancer and associated prognosis </li></ul><ul><li>Age of gestation- fetal viability </li></ul><ul><li>Possible adverse effects of treatment on fetus </li></ul><ul><li>Risk for mother from delay of therapy </li></ul><ul><li>Risk for fetus of premature delivery </li></ul><ul><li>Potential need to terminate the pregnancy </li></ul>
    20. 25. Management of cancer in pregnancy There are not many options and none of them are ideal
    21. 26. <ul><li>To delay treatment until the child </li></ul><ul><li>can be safely delivered </li></ul><ul><li>For mother this poses the risk that may be hard to quantify </li></ul><ul><li>It also means that she will have to care for a very premature </li></ul><ul><li>baby while coping with the side-effects of cancer treatment </li></ul><ul><li>This option is more viable </li></ul><ul><li>the lower the risk posed by the cancer and </li></ul><ul><li>the more advanced the pregnancy </li></ul>First option
    22. 27. <ul><li>To terminate the pregnancy to allow normal </li></ul><ul><li>treatment to go ahead </li></ul><ul><li>This may be the safest option for the mother’s health </li></ul><ul><li>Unacceptable to some mothers </li></ul><ul><li>More likely to be considered early in pregnancy </li></ul>Second option
    23. 28. To treat cancer as effectively as possible while continuing the pregnancy and trying to minimize the risk for fetus Third option
    24. 29. <ul><li>Problems in treatment of cancer in pregnancy </li></ul><ul><li>Late diagnosis </li></ul><ul><li>Damaging effects of radiotherapy </li></ul><ul><li>Consequences of chemotherapy </li></ul>
    25. 30. Cancer in pregnancy if often detected later because the symptoms are masked by other, usually physiological, body changes
    26. 31. <ul><li>Delay in diagnostics </li></ul><ul><li>  </li></ul><ul><li>Presenting symptoms often attributed to pregnancy </li></ul><ul><li>Anatomical and physiological changes of </li></ul><ul><li>pregnancy may compromise the physical examination </li></ul><ul><li>Tumor markers are increased in pregnancy </li></ul><ul><li>(beta HCG, AFP , CA 125 ... ) </li></ul><ul><li>Imaging techniques or invasive procedures </li></ul>
    27. 32. <ul><li>Difficulties in diagnostics & staging </li></ul><ul><li>Some techniques are non-reliable </li></ul><ul><li>Cervical cytology </li></ul><ul><li>Mammogram </li></ul><ul><li>Blood tests- tumor markers </li></ul><ul><li>Some techniques are dangerous </li></ul><ul><li>Abdominal X-rays </li></ul><ul><li>CT </li></ul><ul><li>Radioisotope investigations </li></ul><ul><li>Cervical conisation </li></ul>
    28. 33. <ul><li>Diagnostic procedures that can </li></ul><ul><li>safely be performed in pregnancy: </li></ul><ul><li>Ultrasound </li></ul><ul><li>N uclear mag n etic resonance (NMR) </li></ul>Treatment is often conducted on the basis of incomplete information about the disease !
    29. 34. Risks of radiotherapy Radiotherapy is contraindicated in pregnancy although some specialists use it above the diaphragm with abdominal shielding particularly in later stages of pregnancy
    30. 35. Risks of radiotherapy Therapeutic doses of 5000-6000 cGy expose the fetus to 10 cGy in early pregnancy and 200 cGy or more in later pregnancy Doses over 2,5-5 cGy pose high risk for malformation early in pregnancy
    31. 36. 0 . 05 Gy is limit doses for the risk of malformations. With 1 Gy the risk is 50%
    32. 37. From conception to days 9/10 Letal effect Weeks 2-6 Malformation Growth retardation Weeks 12-16 Mental and growth retardation, microcephaly Weeks 20-25 to birth Sterility, malignancies, genetic disorders Likely effects of radiotherapy
    33. 38. Risks of chemotherapy Almost all drugs cross the placental barrier to some extent As chemotherapeutic drugs work by inhibiting cell division, they pose a risk to the developing fetus.
    34. 39. <ul><li>Risks of chemotherapy </li></ul><ul><li>Chemotherapeutic drugs are associated with: </li></ul><ul><li>Spontaneous abortion </li></ul><ul><li>Malformations </li></ul><ul><li>Teratogenesis </li></ul><ul><li>Mutations </li></ul><ul><li>Carcinogenesis </li></ul><ul><li>Organ toxicity </li></ul><ul><li>Retarded development </li></ul>
    35. 40. Most common drugs reported to induce the malformations or to exert teratogenic effects In « Cancer in Pregnancy », Cambridge 1996 Alkylating agents Antimetabolites Bisulfan Aminopterin Cyclophosphamide Metotrexate Chlorambucil 5-Fluorouracil Cytosine arabinoside
    36. 41. <ul><li>First trimester </li></ul><ul><li>Damage is more likely to occur in the 1 st trimester. </li></ul><ul><li>The rate of chemotherapy –associated fetal malformation </li></ul><ul><li>is 12,7-17% with singl-drug regimens and up to </li></ul><ul><li>25% with combination regimens (general population rate 1-3%) </li></ul><ul><li>Low birth weight occurs in around 40% </li></ul><ul><li>Second and third trimester </li></ul><ul><li>Many drugs pose a relatively low risk </li></ul><ul><li>It is preferable to wait until the development of CNS </li></ul><ul><li>is complete, around 16. weeks </li></ul>Risks of chemotherapy
    37. 42. Delivery If a baby is delivered within 2 weeks of the last chemotherapy dose, there is a risk of a neutropenic baby being born to a neutropenic mother Breastfeading Breast feeding is not advisable for women who have recently been on chemotherapy Risks of chemotherapy
    38. 43. 0.07 - 0.1% of all malignant tumors are diagnosed during or shortly after the pregnancy
    39. 44. What are the most common cancers complicating pregnancy?
    40. 45. The incidence of malignant tumors in pregnancy Cervical cancer 0.17% Breast cancer 0.07% Gastric cancer 0.05% Colon cancer 0.02% Ovarian cancer 0.01%
    41. 46. Genital tumous and pregnancy Cervical cancer Ovarian tumors Endometrial cancer Vaginal cancer Vulvar cancer
    42. 47. Ries LAG, Eisner MP, Kosay CL et al., eds. SEER Cancer Statistics Review, 1975-2001. Bethesda, MD: National Cancer Institute. Available at http://seer.cancer.gov/csr/1975_2001.
    43. 48. <ul><li>Estimated number of cases: 60 ,000 </li></ul><ul><li>Number of deaths: 30 ,000 </li></ul>Burden of cervical cancer, Europe, 2002 Ferlay J, et al. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide, Version 2.0 IARC CancerBases No. 5. Lyon, IARC, 2004.
    44. 49. The disease has been detected during the pregnancy or postpartum period in 1.7 to 3.1%. In reproductive age ≈10% Creasman WT et al., 1970
    45. 50. The incidence of invasive cervical cancer in pregnancy is between 0.3 to 1.6 per 1000 pregnancies
    46. 51. <ul><li>The incidence of cervical pre-cancer </li></ul><ul><li>and invasive cancer in pregnant women </li></ul><ul><li>is similar to the incidence in general population </li></ul><ul><li>Pregnant women (4230) 0.17% </li></ul><ul><li>Non-pregnant women (107 230) 0.18% </li></ul><ul><li>Bokhman JV, 1998. </li></ul>
    47. 52. Screening for invasive cervical cancer should be performed during the first antenatal examination Harper DM, Roach MS. J Fam Pract, 1996; 42: 79-83
    48. 53. Normal pregnancy is not a contraindication for taking cervical smear, nor to colposcopic examination !
    49. 54. Management of abnormal cervical smear during pregnancy Abnormal cytology (5%) Colposcopy B iopsy
    50. 55. Indications for colposcopy <ul><li>Clinically suspicious cervix </li></ul><ul><li>Recurrent and otherwise unexplained bleeding </li></ul><ul><li>Abnormal cervical smear </li></ul><ul><li>The presence of HPV changes </li></ul><ul><li>in cervical smear </li></ul>
    51. 56. The aim of colposcopic examination during the pregnancy is to exclude the invasion !
    52. 57. Ever sion of columnar epithelium
    53. 58. Physiological metaplasia
    54. 59. Decidual rea ction
    55. 60. Decidual pol ypus
    56. 61. HPV in pregnancy
    57. 62. CIN in Pregnancy
    58. 65. The incidence of CIN in pregnancy 0.25 - 1.1 % Bokhman VJ, 1989 0.17 % Kashimura M, 1991 0.93 % Ueki M, 1995 0.3 % Chuquai R, 1994 1.15 % Kesic V, 1996 0.73 %
    59. 66. <ul><li>Conization in pregnancy: </li></ul><ul><li>M icroinvasion confirmed by biops y </li></ul><ul><li>C ytologic suspicion to microinvasive or </li></ul><ul><li>inva sive c an cer </li></ul><ul><li>Large High grade lesion </li></ul><ul><li>Unsatisfactory colposcopic examination </li></ul><ul><li>in histologically proven high grade lesion </li></ul>
    60. 68. Management after the histological finding in pregnancy CIN Mi cro i nvasive cancer Inva sive cancer Conization Postpone further Radi cal d i agnostic and h ysterectomy t herapeutic p rocedures or for post-partum period radiot herapy Targeted biopsy
    61. 69. Conization in pregnancy
    62. 71. <ul><li>Treatment of cervical cancer in pregnancy </li></ul><ul><li>is affected </li></ul><ul><li>by the stage of the disease </li></ul><ul><li>by the age of gestation </li></ul>
    63. 72. The treatment of invasive cervical cancer in pregnancy should proceed without regard for the fetus, unless the lesion is diagnosed at a stage close to fetal viability
    64. 73. <ul><li>Treatment of cervical cancer in pregnancy </li></ul><ul><li>is affected </li></ul><ul><li>by the stage of the disease </li></ul><ul><li>by the age of gestation </li></ul><ul><li>mother’s belief regarding pregnancy termination </li></ul><ul><li>future childbearing desires </li></ul>
    65. 74. Cervical cancer in pregnancy I trimester: Immediate treatment III trimester: Treatment after Caesarean section II trimester ? Medical and ethical problem
    66. 75. Stage Ib/ IIa
    67. 76. Cervical cancer in pregnancy I trimester: Surgery with embryo in utero III trimester: Surgery immediately after Caesarean section II trimester ? Medical and ethical problem
    68. 77. Stage > IIb
    69. 78. Cervical cancer in pregnancy stage > II a I trimester: Start external irradiation Wait for spontaneous abortion III trimester: Caesarean section Irradiation immediately after recovery II trimester ? Medical and ethical problem
    70. 79. Inva sive cervical cancer in second trimester Before 20-24 weeks Evacuating pregnancy by hysterotomy and immediately after radical hysterectomy After 24-28 weeks Waiting for fetal maturity
    71. 80. <ul><li>Delay of treatment for 2-10 weeks </li></ul><ul><li>Sta ge < IIb </li></ul><ul><li>Small tumor </li></ul><ul><li>Gesta tional age > 20 weeks </li></ul><ul><li>van Villet W i sar. Eur J Obst Gynec Reprod Biol, 1998; 79: 153-7 </li></ul>
    72. 81. <ul><li>Karolinska hospital, Stochkolm, Sweden </li></ul><ul><li>Period: 1914-1995 </li></ul><ul><li>19 475 women with cervical carcinoma </li></ul><ul><li>207 (1%) diagnosed in relation with pregnancy </li></ul><ul><li>Mean age 34.3 years (21-47) </li></ul><ul><li>Bjorkholm E & Pettersson F. Carcinoma of the uterine cervix </li></ul><ul><li>and simultaneous pregnancy. </li></ul><ul><li>Int J Gynec Cancer, 1999; 9 (suppl 1): 116 </li></ul>
    73. 82. Karolinska hospital, Stochkolm, Sweden Cervical cancer and simultaneous pregnancy Actuarial survival 1914- 1943: 30.4% 1944- 1959: 53.6% 1969- 1995: 81.5% Bjorkholm E & Pettersson F. Carcinoma of the uterine cervix and simultaneous pregnancy. Int J Gynec Cancer, 1999; 9 (suppl 1): 116
    74. 84. <ul><li>Adnexal masses during pregnancy </li></ul><ul><li>1:1000 deliveries </li></ul><ul><li>Most masses are benign </li></ul><ul><li>Ovarian cancer 1 per 10.000 – 100.000 births </li></ul>Ovarian tumors and the pregnancy
    75. 85. Most frequent types of ovarian tumors in pregnancy Benign c ystic teratom a ................. 36% Ser ous c y stadenom a ................ 25% Muci nous c yst adenom a ................. 12% Corpus luteum cyst ................. 5 . 5% Malign ant tumor s ................ 4%
    76. 86. Ma lignant ovarian tumors and pregnancy In non-pregnant woman 20% ovari an tumo rs are malignant . In pregnancy this percentage is decreased to 5% ( 3% - 9 . 7%) <ul><li>Histological types: </li></ul><ul><li>- Epithelial carcinomas 33-65% </li></ul><ul><li>- Germ-cell tumors 17-40% </li></ul><ul><li>- Sex cord-stromal tumors 9-13% </li></ul>
    77. 87. <ul><li>Malign ant ovarian tumor s and pregnancy </li></ul><ul><li>Only 16% o f o vari an tumor s are detected in </li></ul><ul><li>the first trimester </li></ul><ul><li>20% diagnosed during SC or after delivery </li></ul><ul><li>Almost 25 % have an acute presentation (torsion) </li></ul>If there are no complications, the best timing for surgery of persistant ovarian mass in pregnancy is between 16 to 18 weeks of gestation
    78. 88. If adnexal mass is < 6 cm, unilateral, mobile and asymptomatic: - observation and repeat U/S at 14 to 16 wks. If adnexal mass is > 6 cm, solid or of complex appearance, bilateral or persists into 2nd trimester: - laparotomy. Management of ovarian mass in pregnancy
    79. 89. <ul><li>Prognosis of ovarian cancer in pregnancy </li></ul><ul><li>Similar prognosis to non-pregnant population </li></ul><ul><li>(histology and stage matched) </li></ul><ul><li>Prognosis is quite favourable since most ovarian </li></ul><ul><li>cancers are of low grade and stage </li></ul><ul><li>5-year survival rate: 60-75% </li></ul>
    80. 90. Extra-genital tumous and pregnancy Breast cancer Cancer of the colon Gastric cancer Melanoma Thyroid cancer Bladder cancer Brain tumors Tumors of the hypophysis Hemoblastosis Liver tumors
    81. 91. Incidence of Breast cancer in Europe (sr per 100,000 women) Globocan 2002 … … 36.0 Belaruss 38.8 Russia 44.3 Romania 46.2 Bulgaria 52.1 Macedonija 58.9 B & H 58.9 Slovenia 62.2 Croatia 64.1 Serbia 91.9 France 92.0 Belgium
    82. 92. Breast cancer has been detected during the pregnancy or postpartum period in 3% of cases In reproductive age ≈14%
    83. 93. <ul><li>Breast cancer </li></ul><ul><li>3% of breast cancers is associated with pregnancy </li></ul><ul><li>In the reproductive period patients, breast cancer </li></ul><ul><li>associated with pregnancy in 14% cases </li></ul><ul><li>The incidence of breast cancer in pregnancy is 0,03 </li></ul><ul><li>(1: 3000-1:10 000 pregnancies) </li></ul>
    84. 94. - Mammography sensitivity: 68% (due to increased density ) - Ultrasonography sensitivity: 93% - Open breast biopsy (FNA ±) confirms diagnosis Pregnant woman has 2.5 - fold higher risk to present with advanced disease Diagnosis of Breast Cancer in Pregnancy
    85. 95. <ul><li>Breast cancer in pregnancy </li></ul><ul><li>Delay in starting the treatment is not recommended </li></ul><ul><li>Mastectomy with axillar lymph node dissection </li></ul><ul><li>does not jeoparadise pregnancy </li></ul><ul><li>Conservative surgery ? </li></ul><ul><li>Chemotherapy can be administered in pregnancy </li></ul><ul><li>There is no concensus regarding radiotherapy </li></ul><ul><li>Survival is equal as in non-pregnant patients </li></ul><ul><li>if the stage of the disease is considered </li></ul>
    86. 97. <ul><li>Breast cancer in pregnancy </li></ul><ul><li>Overall survival is worse, because the disease </li></ul><ul><li>is detected in advanced stages </li></ul><ul><li>In 7% pregnant patients with breast cancer, </li></ul><ul><li>the treatment starts within one month after </li></ul><ul><li>diagnosis </li></ul>
    87. 98. <ul><li>Breast cancer in pregnancy </li></ul><ul><li>Later pregnancies do not influence free </li></ul><ul><li>and overall survival </li></ul><ul><li>Next pregnancy should not be planned at least </li></ul><ul><li>for 2 years after the treatment of breast cancer </li></ul>
    88. 99. <ul><li>Cancer in pregnancy: </li></ul><ul><li>common obstetrical, oncological and ethical problems </li></ul><ul><li>Are malignant tumors influencing pregnancy ? </li></ul><ul><li>Is pregnancy influencing the course of malignancy ? </li></ul><ul><li>How to manage the pregnancy ? </li></ul><ul><li>Is metastasing to the placenta and fetus possible ? </li></ul><ul><li>Does pregnancy increase the risk for the development </li></ul><ul><li>of malignancy ? </li></ul><ul><li>Is it necessary to limit the fertility after treatment of' </li></ul><ul><li>malignant tumor? </li></ul>
    89. 100. How frequently does maternal cancer metastasize to either placenta or fetus?
    90. 101. <ul><li>Transfer of fetal cells into the maternal circulation is common and occurs throughout gestation. </li></ul><ul><li>In contrast, transfer of maternal cells (red, white blood cells, platelets) to the fetus is a relatively rare event. </li></ul><ul><li>Tumor cells can rarely involve the products of conception, most likely through the hematogenous route. </li></ul><ul><li>The most common tumor metastasizing to the placenta or fetus is malignant melanoma (almost 30%). </li></ul>The facts we know:
    91. 102. Placenta Estimated incidence of placental involvement by cancer cells: very rare Fetus Estimated incidence of fetal involvement by cancer cells: 25% of the cases with placental involvement
    92. 103. The patient, her partner and her doctor are required to take a difficult decision without always a clear answer (rights of the fetus ≠ rights of the mother) When should therapeutic abortion be recommended?
    93. 104. Therapeutic abortion- general considerations - Absence of guidelines. - Final decision is not always easy - Issue becomes more important when cancer diagnosis is made during the first trimester Most important parameters are: - the stage - the indication for treatment - the curability of the disease.
    94. 105. Recommendations for therapeutic abortion during the first trimester 1. Primary aggressive breast cancer 2. Advanced breast cancer 3. Stage III-IV aggressive NHL or Hodgkin’s disease 4. Acute leukemia
    95. 106. <ul><li>Treatment of cancer in pregnancy requires: </li></ul><ul><li>Evidence-based medicine built on the data </li></ul><ul><li>related to treatment associated risks </li></ul><ul><li>Multidisciplinary approach </li></ul><ul><li>The art of communication with the patient </li></ul><ul><li>High dose of humanity </li></ul>
    96. 107. 1 . Try to benefit mother’s life 2 . Try to treat curable malignant disease of pregnant women 3 . Try to protect fetus and newborn from harmful effects of cancer treatment 4. Try to retain intact mother’s reproductive system for future gestations 4 optimal gold standards to be considered
    97. 108. Obstetrician Gynec olo gist Pa tient Radiotherapist Neonatologist Medical oncologist

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