Cancer in pregnancy march 2012 ghatage co

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Cancer in pregnancy march 2012 ghatage co

  1. 1. Cancer in Pregnancy March 2012 Prafull Ghatage Gynecologic Oncologist Tom Baker Cancer Centre Calgary, CANADA.
  2. 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. 3. The occurrence of cancer in pregnancy is rare, about 1 case per 1000 deliveries
  4. 4. The Dilemma ? Save the mother ? Save the baby Malignant disease in pregnancy complicates the management of both cancer and the pregnancy.
  5. 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. 6. Fetus Mother Pregnancy Risk
  7. 7. Management of cancer in pregnancy There are not many options and none of them are ideal
  8. 8. For women diagnosed with cancer waiting for 40 weeks could be a death sentence particularly with high-grade, aggressive or metastatic cancers.
  9. 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. 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. 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. 12. Problems in treatment of cancer in pregnancy •  Late diagnosis •  Damaging effects of radiotherapy •  Consequences of chemotherapy
  13. 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. 14. Cancer in pregnancy is often detected later because the symptoms are masked by other, usually physiological, body changes
  15. 15. Cancer in young women Site Age 15-44 (%) Cervix 35 Ovary 15 Lymphoma 23 Thyroid 50 Melanoma 27 Breast 15 Leukemia 10
  16. 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. 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. 18. Diagnostic procedures that are SAFE in pregnancy: •  Ultrasound • Magnetic resonance imaging (MRI)
  19. 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. 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. 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. 22. Radiotherapy •  Contraindicated in pregnancy •  Possible in early pregnancy with lead shielding •  Maybe also consider in late pregnancy for the chest with shielding
  23. 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. 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. 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. 26. Risks of chemotherapy •  Spontaneous abortion •  Malformations •  Teratogenesis •  Mutations •  Carcinogenesis •  Organ toxicity •  Retarded development
  27. 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. 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. 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. 30. Pre-invasive and invasive cervical cancer in pregnancy
  31. 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. 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. 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. 34. Management of abnormal cervical smear during pregnancy Pregnancy is not a contraindication for a pap smear Abnormal cytology (5%) Colposcopy Biopsy
  35. 35. Indications for colposcopy •  Clinically SUSPICIOUS cervix •  Recurrent and otherwise unexplained BLEEDING •  ABNORMAL pap
  36. 36. The aim of colposcopic examination during the pregnancy is to exclude invasion
  37. 37. Normal cervix in pregnancy
  38. 38. Normal cervix at 24 weeks
  39. 39. HPV in pregnancy
  40. 40. CIN III in pregnancy (ASCPP)
  41. 41. Microglandular Hyperplasia
  42. 42. Microinvasive cancer (ASCCP)
  43. 43. Early invasive cancer (ASCCP)
  44. 44. Decidual reaction
  45. 45. Conization in pregnancy •  MICROINVASION confirmed by biopsy •  Pap suggestive of INVASION •  ??? Unsatisfactory colposcopic examination in a histologically proven high grade lesion
  46. 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. 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. 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. 49. Stage Ib/ IIa
  50. 50. Cervical cancer in pregnancy I trimester: Surgery with embryo in utero III trimester: Radical Caesarean hysterectomy II trimester ? Medical and ethical problem
  51. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 64. Conclusion •  Malignancy is rare in pregnancy •  Consideration of mother and fetus •  Close coordination also required between patient, obstetrician, neonatologist and oncologist

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