Cancer in pregnancy march 2012 ghatage co

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  • 1. Cancer in Pregnancy March 2012 Prafull Ghatage Gynecologic Oncologist Tom Baker Cancer Centre Calgary, CANADA.
  • 2. Learning Objectives •  Incidence •  Investigations and management issues •  Risks of surgery •  Risks of radiotherapy •  Risks of chemotherapy •  Termination - ? Necessary / Advantageous •  If delivery - ? how / ? When •  Future pregnancies
  • 3. The occurrence of cancer in pregnancy is rare, about 1 case per 1000 deliveries
  • 4. The Dilemma ? Save the mother ? Save the baby Malignant disease in pregnancy complicates the management of both cancer and the pregnancy.
  • 5. Is the potential life of an unborn child more important than prolonging a life of a young woman? And whose decision is this ? ?
  • 6. Fetus Mother Pregnancy Risk
  • 7. Management of cancer in pregnancy There are not many options and none of them are ideal
  • 8. For women diagnosed with cancer waiting for 40 weeks could be a death sentence particularly with high-grade, aggressive or metastatic cancers.
  • 9. To delay treatment until the child can be safely delivered •  For mother this poses the risk that may be hard to quantify •  It also means that she will have to care for a very premature baby while coping with the side-effects of cancer treatment This option is more viable the lower the risk posed by the cancer and the more advanced the pregnancy First option
  • 10. To terminate the pregnancy to allow normal treatment to go ahead •  This may be the safest option for the mother s health •  Unacceptable to some mothers More likely to be considered early in pregnancy Second option
  • 11. To treat the cancer as effectively as possible while continuing the pregnancy and trying to minimize the risk for the fetus Third option
  • 12. Problems in treatment of cancer in pregnancy •  Late diagnosis •  Damaging effects of radiotherapy •  Consequences of chemotherapy
  • 13. Delay in diagnostics •  Presenting symptoms often attributed to pregnancy •  Anatomical and physiological changes of pregnancy may compromise the physical examination •  Tumor markers are increased in pregnancy (beta HCG, AFP, CA 125... ) •  Imaging techniques or invasive procedures
  • 14. Cancer in pregnancy is often detected later because the symptoms are masked by other, usually physiological, body changes
  • 15. Cancer in young women Site Age 15-44 (%) Cervix 35 Ovary 15 Lymphoma 23 Thyroid 50 Melanoma 27 Breast 15 Leukemia 10
  • 16. Cancer incidence in Pregnancy Site Est. incidence / 1000 pregnancies Cervix Non-invasive Invasive 1.3-1.7 1.0 Breast 0.33 – 0.7 Melanoma 0.14 Ovary 0.10 ( 0.01%) Thyroid Unknown Lymphoma 0.01 Leukemia 0.01 Colon 0.20
  • 17. Factors influencing the management of pregnant women diagnosed with cancer • Stage of cancer and associated prognosis •  Age of gestation- fetal viability •  Possible adverse effects of treatment on fetus •  Risk for mother from delay of therapy •  Risk for fetus of premature delivery •  Potential need to terminate the pregnancy
  • 18. Diagnostic procedures that are SAFE in pregnancy: •  Ultrasound • Magnetic resonance imaging (MRI)
  • 19. Difficulties in diagnostics & staging Some techniques are unreliable •  Mammogram •  Blood tests- tumor markers Some techniques are dangerous •  CT scan •  Radioisotope investigations •  Cervical conisation
  • 20. Effective Radiation dose with background radiation exposure Procedure Radiation dose in millisieverts Comparable to background radiation for: Additional lifetime risk of fetal cancer CXR 0.1 5 years Low Abdominal XR 2.2 9 months Very low CT abd/ Pelvis 15 5 years Low CT abd/pelvis with contrast 30 10 years Moderate Mammogram 0.4 7 weeks Very low 1 cGy = 1J/kg; 1 Sv = 1J/kg.
  • 21. Three stages of Embryogenesis •  I – First 2 weeks – Blastocyst resistant to teratogens. Blastocyst has NOT differentiated. •  II – Organogenesis – 3rd to 8th week. Maximal teratogenesis. Ends by 13th week •  III – Increase in fetal and organ size. CNS development complete by 16 weeks. Brain and gonadal tissue will continue to develop. Teratogens will cause IUGR but no organ malformation
  • 22. Radiotherapy •  Contraindicated in pregnancy •  Possible in early pregnancy with lead shielding •  Maybe also consider in late pregnancy for the chest with shielding
  • 23. 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 With 10 cGy the risk is 50%
  • 24. Conception to days 9/10 Lethal Weeks 2-6 Malformation Growth retardation Weeks 12-16 Mental and growth retardation, microcephaly Weeks 20-25 to birth Sterility, malignancies, genetic disorders Effects of radiotherapy
  • 25. 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.
  • 26. Risks of chemotherapy •  Spontaneous abortion •  Malformations •  Teratogenesis •  Mutations •  Carcinogenesis •  Organ toxicity •  Retarded development
  • 27. First trimester •  Most likely in the 1st trimester. •  Fetal malformation rate 12.7-17% with single-drug regimens and up to 25% with combination regimens (cf - general population rate 1-3%) •  Low birth weight ~ 40% Second and third trimester •  Relatively low risk •  It is preferable to wait until the development of CNS is complete, around 16 weeks Risks of chemotherapy
  • 28. 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 Breastfeeding Breast feeding is not advisable for women who have recently been on chemotherapy Risks of chemotherapy
  • 29. Lancet Oncology ,Amant et al, Feb 2012 •  68 pregnancies •  236 cycles of chemotherapy •  Safe in the 2nd and 3rd trimester •  No association with CNS, Cardiac or Auditory morbidity. Risks of chemotherapy
  • 30. Pre-invasive and invasive cervical cancer in pregnancy
  • 31. Incidence of cervical pre-invasive and invasive cancer in pregnant women is similar to the incidence in general population Pregnant women (4230) 0.17% Non-pregnant women (107230) 0.18% Bokhman JV, 1998.
  • 32. 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
  • 33. Screening for invasive cervical cancer should be performed during the first antenatal examination Harper DM, Roach MS. J Fam Pract, 1996; 42: 79-83
  • 34. Management of abnormal cervical smear during pregnancy Pregnancy is not a contraindication for a pap smear Abnormal cytology (5%) Colposcopy Biopsy
  • 35. Indications for colposcopy •  Clinically SUSPICIOUS cervix •  Recurrent and otherwise unexplained BLEEDING •  ABNORMAL pap
  • 36. The aim of colposcopic examination during the pregnancy is to exclude invasion
  • 37. Normal cervix in pregnancy
  • 38. Normal cervix at 24 weeks
  • 39. HPV in pregnancy
  • 40. CIN III in pregnancy (ASCPP)
  • 41. Microglandular Hyperplasia
  • 42. Microinvasive cancer (ASCCP)
  • 43. Early invasive cancer (ASCCP)
  • 44. Decidual reaction
  • 45. Conization in pregnancy •  MICROINVASION confirmed by biopsy •  Pap suggestive of INVASION •  ??? Unsatisfactory colposcopic examination in a histologically proven high grade lesion
  • 46. Management after the histological finding in pregnancy CIN Microinvasive cancer Invasive cancer Conization Postpone further Radical diagnostic and hysterectomy therapeutic procedures or for post-partum period radiotherapy Targeted biopsy
  • 47. Treatment of cervical cancer in pregnancy is affected •  by the stage of the disease •  by the age of gestation •  mother’s belief regarding pregnancy termination •  future childbearing desires
  • 48. 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
  • 49. Stage Ib/ IIa
  • 50. Cervical cancer in pregnancy I trimester: Surgery with embryo in utero III trimester: Radical Caesarean hysterectomy II trimester ? Medical and ethical problem
  • 51. Invasive 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
  • 52. Delay of treatment for 2-10 weeks •  Small tumor •  Stage < IIB •  Gestational age > 20 weeks van Villet W i sar. Eur J Obst Gynec Reprod Biol, 1998; 79: 153-7
  • 53. Adnexal masses during pregnancy 1:1000 deliveries Most masses are benign. Malignant tumors are generally low grade and stage with survival of 75% Ovarian cancer 1 per 10.000 – 100.000 births Ovarian tumors and the pregnancy
  • 54. Most frequent types of ovarian tumors in pregnancy Benign cystic teratoma ................. 36% Serous cystadenoma ................ 25% Mucinous cystadenoma ................. 12% Corpus luteum cyst ................. 5.5% Malignant tumors ................ 4%
  • 55. Malignant ovarian tumors and pregnancy In non-pregnant woman 20% ovarian tumors are malignant. In pregnancy this percentage is decreased to 5% ( 3% - 9.7%) - - Epithelial carcinomas 33-65% - - Germ-cell tumors 17-40% - - Sex cord-stromal tumors 9-13%
  • 56. Malignant ovarian tumors and pregnancy •  Only 16% of ovarian tumors detected in the first trimester •  20% diagnosed during CS or after delivery •  Almost 25% have an acute presentation (torsion) If there are no complications, the best timing for surgery of persistent ovarian mass in pregnancy is between 16 to18 weeks of gestation
  • 57. If adnexal mass is < 8 cm, unilateral, mobile and asymptomatic: - observation and repeat U/S at 14 to 16 weeks. If adnexal mass is > 8 cm, solid or of complex appearance, bilateral or persists into 2nd trimester: - laparotomy Management of ovarian mass in pregnancy
  • 58. Breast cancer •  3% of breast cancers is associated with pregnancy •  In the reproductive period patients, breast cancer associated with pregnancy in 14% cases •  The incidence of breast cancer in pregnancy is 0.03 (1: 3000-1:10 000 pregnancies) •  Pregnant women have a 2.5 fold higher risk to present with advanced cancer
  • 59. Breast cancer in pregnancy •  Delay in starting the treatment is not recommended •  Mastectomy with axillary lymph node dissection does not jeopardise pregnancy •  Conservative surgery ? •  Chemotherapy can be administered in pregnancy •  There is no consensus regarding radiotherapy Survival is equal as in non-pregnant patients if the stage of the disease is considered
  • 60. Breast cancer in pregnancy •  Later pregnancies do not influence overall survival •  Next pregnancy should not be planned at least for 2 years after treatment
  • 61. 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?
  • 62. 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.
  • 63. 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
  • 64. Conclusion •  Malignancy is rare in pregnancy •  Consideration of mother and fetus •  Close coordination also required between patient, obstetrician, neonatologist and oncologist