Cancer during pregnancy can present challenges for balancing treatment of the mother's cancer while protecting the fetus. Key points include: - Treatment should not differ between pregnant and non-pregnant women when feasible, and aim to benefit the mother's life while protecting the fetus from harmful effects. - The most common cancers in pregnant women are melanoma, breast cancer, thyroid cancer, and gynecological or blood cancers. - For imaging, ultrasound and MRI are preferred over X-rays, CT scans, and PET scans to minimize radiation exposure to the fetus. - For breast cancer, surgery is usually the initial treatment. Chemotherapy can be used in the 2nd and 3rd trimesters for

1. Cancer during Pregnancy
-Dr. Sanketh Kotne
M.D(Radiation Oncology) D.M. (Medical Oncology)

2. ● Treatment should not differ between pregnant and not
pregnant women, if feasible.
● Should aim for optimal maternal treatment and
safeguard foetal well-being (when both are compatible)
● Trend for delaying pregnancy into the later reproductive
years: expected to see more cases of cancer
complicating pregnancy
● Medical, ethical, psychological and religious issues

3. Optimum Gold Standards
● To try to benefit mother’s life
● To try to treat curable malignant disease of pregnant
women
● To try to protect foetus and new-born from harmful
effects of cancer treatment
● Try to retain the mother’s reproductive system intact
for future gestations

4. Incidence
● The occurrence of cancer in a pregnant woman is relatively rare
(0.07 - 0.1% of all malignant tumors)
● 1 in every 1000 pregnant women is diagnosed with cancer
● The most common cancers were melanoma of skin, breast
cancer, thyroid and other endocrine cancers, gynecological and
lymphohaematopoeitic cancers.

6. Oncologic Issue Obstetrical Issues
● Type of therapy Antepartum fetal surveillance
● Timing of therapy Corticosteroid use
● Maternal effects of therapy Amniocentesis
● Maternal outcomes Timing of delivery
● Fetal effects of therapy Route of delivery

7. Ethical, Religious, Legal & Socio-economic
Issues
Berman, DiSaia & Tewari. Ch 58, Maternal-Fetal Medicine, 5th Ed, Creasy & Resnik (eds), 2004
● Pregnancy termination
● Fetal viability
● Maternal risk / future fertility
● Health-care costs & expenditure
● Right to autonomy
● Mother’s overall prognosis

8. Gestational Age and Effects of Antineoplastic
Therapy
Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N; ESMO Guidelines Working Group.
Ann Oncol. 2010 May;21 Suppl 5:v266-73.

10. SERUM TUMOR MARKERS
Tewari Ch 16, Clinical Gynecologic Oncology, 7th Ed, DiSaia & Creasman (eds) 2007

11. • Not reliable
• They have no diagnostic value and consequently
• They should not be performed during pregnancy
SERUM TUMOR MARKERS
Pregnant & Non-Pregnant Patients

12. Chemotherapy during pregnancy
● Most drugs with MW<600 KDa are capable of crossing the placenta.
● Changes in pregnancy:
■ Increased plasma volume
■ increased renal clearance of drugs
■ faster hepatic oxidation
■ reduced albumin levels
■ third space (amniotic fluid)
● Most toxic effects were reported during embryogenesis in the 1st
trimester
● Data on the teratogenic risks of chemotherapy are based on case
reports and retrospective series.
*More data are needed

13. Effects of chemotherapy by
gestational stage

14. Effects & Risks after Exposure to
Ionizing Radiation in Utero
Zagouri F, et al. ESMO Open 2016;1:e000016. doi:10.1136/esmoopen-2015-000016

15. Tewari Ch 16, Clinical Gynecologic Oncology, 7th Ed, DiSaia & Creasman (eds) 2007

16. STAGING
● Staging examinations are performed as in nonpregnant women
and are important.
● Ultrasonography and MRI techniques are preferred
● No documented deleterious effects of MRI exposure on the
developing fetus in any trimester of pregnancy
[Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy.Maternal and Fetal Risks. Cambridge:
Cambridge University Press, 1996.]

17. Recommendations
● Limited to those associated with the lowest exposure to ionising
radiation
● Abdominal plain films, Isotope scans, PET scans and CT-
scans should be avoided.
● Chest X-ray (with lead apron) and abdominal ultrasound can be
indicated and are safe.
● Gadolinium crosses the placenta and causes foetal
abnormalities in rats. MRI causes heating/cavitation in early
embryos→ Use of gadolinium during pregnancy is
contraindicated, especially in the 1st trimester [Nicklas et al. , Semin
Oncol 2000;27:623:]

18. Breast cancer associated with
pregnancy

19. Clinical presentation
● Painless lump is the most frequent presentation.
● Present with advanced diseases :B'coz of the physiological modifications of
the breast in pregnancy-- small lumps cannot be easily detected due to the
natural tenderness and engorgement of the breasts during pregnancy and
lactation
● Pregnant women have a 2.5 - fold higher risk to present with advanced disease

20. Diagnosis
● During the 1st trimester of pregnancy, only absolutely
necessary radiological work-up is justified.
● Mammography sensitivity: 68% (due to increased density and
congestion)
● Ultrasonography sensitivity: 93%
● FNA, Open or Core Needle breast biopsy confirms diagnosis-
Core biopsy preferred.
● No differences in various histologic types

21. ● Mammography: possible with proper shielding of the abdomen
● With a two-view mammogram the uterine-fetal dose is 4 mGy, well
below the threshold for deterministic effects of 100 mGy in order to
rule out diffuse microcalcifications
● A single projection can be considered to reduce radiation exposure.
● MRI: Not been investigated adequately.
● However, the use of gadolinium contrast media is discouraged, as the
contrast media cross the placenta and induce malformations in
animal models (Garel et al. 1998).
● Thus the routine use of breast MRI during pregnancy is discouraged.

22. ● Chest X-ray seems safe with appropriate radioprotection (lead
apron).
● Radionuclide isotope scans and CT scans should be avoided
● For imaging of the brain, liver, or bones in the context of clinical
suspicion for metastases, MRI has been advocated.

23. SURGERY :Mastectomy Vs
Breast-Conserving Therapy
● Historically, mastectomy was considered to be the standard surgical
procedure in pregnant patients with breast cancer.
● Reasons :
1) Patients frequently presented with large tumors.
2) Concern about the delay before giving Radiotherapy, which is
contraindicated.
● It is important to inform the patient that mastectomy is not mandatory (Schwartz
et al. 2006)
● 2nd or 3rd trimester: the surgical approach applied to women should not
significantly differ.
● 1st trimester : MRM - SOC in the 1st trimester ; who wants to continue the
pregnancy and also wishes to conserve the breast all the issues have to be
carefully discussed, and the informed that a possible increased risk of local
recurrence should be considered, even though this is difficult to quantify because
of the lack of data.

24. ● Lymphoscintigraphy and SLNB can be safely performed during
pregnancy, without any significant risks to the fetus at any phase of
pregnancy.
● Maximum absorbed dose with 92.5 MBq (2.5 mCi) of 99mTc-sulfur
colloid : 0.0043 Gy
● Blue dye is contradicted - potential allergic reactions (2%)

25. ● It is likely that Larger tumors and more frequent
involvement of the regional lymph nodes, breast cancers in
pregnancy are characterized by poor differentiation and
low expression of ER & PR (Bonnier et al. 1997; Gentilini et al. 2004;
Middleton et al. 2003; Miller et al. 2005; Reed et al. 2003; Ring et al. 2005)

26. Adjuvant Therapies
● The indications for adjuvant chemotherapy in
pregnant patients are identical to those in
nonpregnant patients

27. Early Breast Cancer (Stages I and II)
● MRM is the treatment of choice for stage I and stage II breast cancer.
● Radiotherapy should be delayed until after delivery in order to
avoid harmful effects on the fetus.
● Adjuvant Chemotherapy, if indicated, should not be administered
during the 1st trimester of gestation.
● Petrek et al., the 5-year survival of patients with negative axillary nodes was
82% in both pregnant and nonpregnant women, while the 10-year survival
was 77% for pregnant and 75% for nonpregnant women. No statistically
significant treatment effect was noted

28. ● Chemotherapy is contraindicated in the 1st trimester: vulnerable to
the teratogenic effects of chemotherapy
● The timing of chemotherapy is crucial: While it is obviously preferable
to postpone chemotherapy until after delivery, this is not always
possible.
● Locally advanced tumors may need to be treated in a Neoadjuvant
manner.
● Patients whose tumors do not express estrogen receptors, a late start
of chemotherapy, that is, >3 weeks after surgery, may worsen the
prognosis dramatically as compared to an early start of
chemotherapy
● Thus chemotherapy may need to be started during pregnancy even in
patients with estrogen receptor-positive tumors

29. ● In the 2nd and 3rd trimesters Chemotherapy is relatively safe[M.D.
Anderson Cancer Center (Hahn et al. 2006) and from the Royal Marsden Hospital (Ring et al.
2005)]
● Doxorubicin,Cyclophosphamide, and Fluorouracil have been used in
a reasonably large number of patients and may be considered safe
for use after the 1st trimester of pregnancy.

31. ● No definite and consistent adverse fetal effects have been observed
with Taxanes - their safety record is very limited.
● shown minimal transplacental transfer of both agents, probably due to the high
expression of P-glycoprotein in the placenta
● Data is available with the use of paclitaxel than of docetaxel during
pregnancy.
● Weekly paclitaxel schedule is the preferred treatment option in selected
cases of patients with breast cancer during pregnancy
Why weekly?
•Allow close monitoring of pregnancy
•Low peak plasma concentration resulting in
• Lower toxicity (more safe)
• Possible lower placental transfer & foetal exposure
•Easy interruption in case of toxicity
•Efficacy of weekly regimens is established outside pregnancy

32. ● Trastuzumab is known to cross the placenta -? Anhydramnios
● It interferes with VEGF signalling responsible for amniotic fluid production
and reabsorption
● At the present time, it seems prudent to consider the efficacy of the
sequential use of chemotherapy and trastuzumab and to defer the
adjuvant therapy with trastuzumab to the postpartum period.
● For women becoming accidentally pregnant while on trastuzumab
administration- Preserve their pregnancy & discontinue
•Pertuzumab is contraindicated during pregnancy.
•Limited data for its toxicity.
•Massive transplacental transfer

33. ● Tamoxifen - reported to cause malformations of the genital tract
and of the skeleton the development of the uterus was impaired
after exposure to tamoxifen (resembling the changes induced
by diethylstilbestrol)
● At present, Adjuvant therapy with tamoxifen should be started
after pregnancy.

34. Advanced Breast Cancer (Stages III
and IV)
● Chemotherapy is still indicated after the 1st trimester of
pregnancy
● Neoadjuvant chemotherapy may be indicated for the therapy of
locally advanced breast cancer.

35. ● Biphosphonates :
● Preclinical models: cross the placenta; the fetal
osteoclastactivity could be inhibited, giving rise to Skeletal
deformities, genital defects
● Induced Maternal hypocalcaemia: Affects uterine contraction
● A systematic review of literature till 09-200852 patients exposed (mainly
osteoporosis): Normal outcomes[Patlas N et al. Teratology 1999;60(2):68-73; Ornoy A et al. Reprod
Toxicol 2006;21(4):446-457; Djokanovic N et al. J Obstet Gynaecol Can 2008;30(6):505-507]
● Use of bisphosphonates is not recommended during pregnancy

36. Vomiting and nausea - metoclopramide is the first choice for these
symptoms, whereas ondansetron can safely be given.
G-CSF: can cross the human placenta at least in the 2nd and 3rd
trimesters. considered as agent belonging in category C for use
during pregnancy.
use should be based on clinical necessity
Ondansetron, Lorazepam and Dexamethasone: can be safely
given as pre-chemo antiemetic regimen

38. Radiotherapy
● Dilemma ! whether or not to administer radiotherapy during the 1st or
early in the 2nd trimester.
● If patient wants conserve her breast ,it is appropriate,But then there is
the question of giving postoperative radiotherapy before delivery, or
delaying it until later.
● Delaying radiotherapy in the management of breast cancer is
likely to lead to an increased rate of local recurrence
● In patients diagnosed later on in the pregnancy,Radiotherapy could
well be postponed until after delivery without detrimental effects to the
maternal outcome

39. ● Dose to a foetus resulting from tangential breast irradiation, measured using
anthropomorphic phantoms simulating the geometry of a pregnant woman, has
been calculated for all trimesters of gestation.[Mazonakis M, Varveris H, Damilakis J, et al.
Radiation dose to conceptus resulting from tangential breast irradiation. Int J Radiat Oncol Biol Phys
2003;55(2):386–91.]
● The dose increased as the pregnancy became more advanced, because of the
increased proximity of the foetus to the primary irradiation field.

40. Techniques to Estimate & Reduce Foetal
Dose
Two types of shielding arrangements
● Bridge over Patient:
● A basic shield design consists of a bridge over the patient’s
abdomen with a block of lead or other shielding material
● Thickness of 5HVL
● The superior edge of the block must be positioned as near as
possible to the inferior edge of the treatment field. This position
easily attenuates much of the dose contribution due to head
leakage and collimator scatter.
● For the treatment of a posterior field, the patient may lie prone on
a false table top, with the shielding bridge placed over her back.

41. ● Mobile Shields:
● Treatment versatility can be increased by coupling the basic
bridge over patient design with a frame which supports the lead
block such that it does not rest upon the treatment couch.
● Additionally, a vertical adjustment motor is added to allow for
treatment at source-to-skin distance of 80−125 cm and
appropriate wheels are attached to allow for easy movement by
the treatment staff. The addition of side shielding allows for the
treatment of lateral fields
● For posterior fields, a shield fits between the treatment couch and
head of the treatment machine. Although the shield is attached to
the treatment couch, the contribution of shield and patient weight
typically will not exceed the limits defined by the manufacturer.

45. ● With shielding, 50–75% dose reduction can be achieved [Kal HB, Struikmans H.
Radiotherapy during pregnancy: fact and fiction. Lancet Oncol 2005;6(5):328–33; Han B, Bednarz B, Xu XG.
A study of the shielding used to reduce leakage and scattered radiation to the fetus in a pregnant patient
treated with a 6-MV external X-ray beam.Health Phys 2009;97(6):581–9.]
● Thus, during the 1st and the 2nd trimester of pregnancy, the fetal irradiation
dose is considerably lower than the threshold values associated organ
malformations. During the 3rd trimester, however, the dose seems to exceed
● In utero irradiation at all gestational ages may increase the risk of
cancer during childhood.
● A conservative estimate of the lifetime risk of radiation induced by
fetal exposure to 0.01 Gy is about 1 in 1700 cases.
● Therefore, Radiotherapy is considered relatively safe only during the
1st and 2nd trimester of pregnancy, if at all.

49. ● The most used regimens are 5-fluorouracil (F)-doxorubicin (A) or
epirubicin(E)- cyclophosphamide(C) or AC
● the Panel considers currently used cytotoxic drugs for breast cancer
relatively safe for use during pregnancy. There are insufficient data to
propose one preferred regimen based on safety.
● Regimens that could be used in the Neoadjuvant setting include
FEC, EC, FAC, AC and T
● CMF should not be used during pregnancy

50. Important issues of prenatal care, in
particular relating to the use of chemotherapy?
● To correctly estimate the fetal risk caused by the mother’s cancer
treatment
● Before starting staging examinations and treatment, USG of the foetus
should be performed -to ensure that the foetus has undergone normal
development and growth to date.
● Before every cycle of cytotoxic treatment, an evaluation of fetal
morphology, growth and well being must be carried out by ultrasound
screening, if indicated with Doppler
● In case of abnormal findings a more intense fetal monitoring or even
(preterm) delivery may be required.
● The timing of delivery should be balanced according to the oncological
treatment schedule and the maturation of the foetus

51. ● If continuation of therapy is required postpartum, a vaginal delivery is
recommended since this is associated with a lower risk of therapy delay due
to lower maternal morbidity.
● To allow the bone marrow to recover and to minimise the risk of maternal
and fetal neutropenia, delivery should be planned 3 weeks after the last dose
of anthracycline-based chemotherapy
● Chemotherapy should not be administered after 35 weeks since
spontaneous labour becomes more likely. This policy minimizes the risk of
neutropenia at the time of delivery.
● Chemotherapy can be restarted when needed after delivery.
● An interval of 1 week after an uncomplicated caesarean section is needed.
● Breastfeeding shortly after chemotherapy is not recommended. Primary
inhibition of milk production is needed because especially lipophylic agents
as taxanes can accumulate in the milk.

52. “ABORTION DOES NOT IMPROVE PROGNOSIS”
● 1950s and 1960s :
● therapeutic abortion was advocated
● Due to concerns for hormonal stimulation of tumor growth or to
lack of effective systemic therapy
● 1980s and 1990s :
● Therapeutic abortion failed to improve survival, and it was found
that pregnancy had no effect on the course of the disease.
● 80% of pregnancy- associated breast cancers were ER,PR Neg.
● Should consider therapeutic abortion during the 1st and 2nd
trimesters only in Aggressive primary breast cancer or in patients with
advanced disease, in which prompt treatment is strongly
recommended.

53. Subsequent Pregnancy
● Patients with early stage disease (stage I-II), a delay of at least
2 years is necessary
● Patients with stage III should be deferring pregnancy for at least
5-years
● Patients with stage IV should not consider conception at all
● In BRCA1 or BRCA2 carriers :should not be discouraged because of
the concern that it may increase breast cancer incidence. Breast-
feeding could be protective in BRCA1 carriers.

54. Cervix cancer
● Incidence: 0.02% -0.9%.
● Up to 40% of reproductive age women have HPV
● 2.0-6.5% cases of CIN/SIL occur in pregnant women
● HPV in pregnancy, as prevalent as compared to the
nonpregnant population, and might be increased.
● In HPV+ women, increased parity is recognized as an
independent increase risk factor for cervical squamous
carcinomas (Munoz 2002)

55. Although the diagnosis of cervical cancer in pregnancy can
sometimes be delayed,
●Adequate evidence that pregnant women have a 3.1-fold
higher chance of being diagnosed with stage I disease
because of frequent pelvic examinations.

56. Screening for Cervical Cancer/SIL
● Often a delay in diagnosis (fear of biopsies)
● Pap smear at registration and 8 weeks postpartum
− Ectocervical scrape
− Endocervical swab / brush – risky
− HPV typing
● Pap less accurate in pregnancy:
● Increased false negative rate
− Blood, inflammation
− Failure to sample SCJ
− Concern about bleeding
− Difficult to see cervix
− Absence of endocervical cells

57. Presentation
● Abnormal smear
● Post-coital bleeding
● Frank malignancy noted on examination
● Abnormal vaginal bleeding during pregnancy
● Detection at examination in labor
● Abnormal post-partum bleeding
● Histological proof of cancer is mandatory. Obtained by with
punch biopsy, loop cone biopsy or wedge biopsy

58. Diagnosis of SIL and Cervical
Cancer
● Careful palpation of cervix
● Biopsy all suspicious lesions: even if Pap/HPV are neg
● Abnormal Pap:
● ASCUS/LSIL and HPV negative – repeat post partum
● ASCUS/LSIL and HPV positive: colposcopy
● ASC-H: Colposcopy
● HSIL: Colposcopy
● Don’t defer biopsy because of fear of bleeding or preterm labor.
1st trimester easiest
● Control bleeding with:Pressure, Monsell’s solution (Ferric subsulfate),
Silver nitrate

59. Management of Cervical SIL On
Biopsy
Satisfactory Colposcopy
●LSIL / HPV+/- :
− Re-evaluate 6-8 weeks postpartum
− 50% regress postpartum: Delivery
●HSIL / HPV+/- :
− Follow up depends on trimester
− 30% regress postpartum
− Vaginal delivery OK

60. ● Cone biopsy in pregnancy
● Indications
− Unsatisfactory colposcopy/ Pap: SCC
− Adenocarcinoma in situ
− Microinvasive SCC
• Perform between 14 and 20 weeks
● Risks
− Abortion: 5%
− Hemorrhage: immediate: 9%, delayed: 4%
● Technique
● Local wedge resection
● Shallow cone
● LEEP
● Vasopressin/ local anesthetic with epinephrine

61. Treatment
?
??

62. Carcinoma in-situ:
● Pregnancy is allowed to reach full term
● Re-evaluation and definitive therapy- completed 6-8 weeks following delivery
● Risk of progression to invasive carcinoma - 0 to 0.4 %
● Confirmation by colposcopy and conservative management with monthly pap
smears.
● Route of delivery should be based on standard obstetrical indications
● Conization is frequently performed.
● 50% have residual after delivery.

63. Stage IA1
● Conization (Coin excision): no further treatment necessary
● Vaginal delivery at term
● Simple hysterectomy post-partum or Cesarian hysterectomy at
term
● Risk of bleeding (5 -15%); risk of spontaneous abortion(upto 15%)

64. Stage IA2, IB & IIA
● Vaginal delivery: increased risk of hemorrhage and cervical laceration
● Depends on desire for pregnancy
● 1st trimester:
− Delay of up to 28 weeks: degree of risk unknown
− Radical hysterectomy and pelvic LND at diagnosis
− Radical cone biopsy/ trachelectomy/ cerclage and
extraperitoneal pelvic and aortic LND at 16-18 weeks
− C-Section and Radical hysterectomy and pelvic LND when
mature.
● 2nd trimester:
− Delay of up to 22 weeks
− Can probably safely wait until maturity
● 3rd trimester:
− Delay of up to 10 weeks
− C-section, Radical hysterectomy and pelvic Lymph node dissection
at maturity

65. Stage IB (bulky) or Stages IIb-IV:
1st trimester :
● Delay of up to 28 weeks
● Depends on desire for pregnancy
● Unwanted pregnancy:
− Whole pelvic radiation therapy/ chemotherapy
− If SAB occurs before XRT is finished – proceed with
brachytherapy
− Occasionally will need hysterotomy and pelvic LND if no SAB
and then brachytherapy ; or a “small” radical hyst. & pelvic
LND if small residual cervical disease.
● Wanted pregnancy:
− Consider chemotherapy until maturity at 34 weeks

66. 2nd trimester:
● Delay of up to 22 weeks
● Unwanted pregnancy
− Radiation therapy
− Spontaneous abortion at 35 days
● Wanted pregnancy
− consider chemotherapy until maturity
3rd trimester :
● Delay of up to 10 weeks
● C-Section at maturity/ staging lap; transpose ovaries
● Start radiation therapy 2 weeks postpartum
● Consider chemotherapy until maturity

67. Pregnancy Non-preserving
Management
● Advanced-stage disease: Termination of pregnancy and subsequent
standard treatment are advocated.
● Radical hysterectomy with fetus in utero during early pregnancy or after
hysterotomy.
● Pelvic radiotherapy causes spontaneous abortion during the 1st trimester
and fetal death within the first month after external beam radiation during the
2nd trimester.
● The advantages and disadvantages of hysterotomy before radiotherapy
should individually be balanced.
● When hysterotomy is performed before initiating radiotherapy
● Less obstetrical complications (bleeding and diffuse intravascular
coagulation),
● Less psychologic distress.
● May be associated with postoperative adhesions that enhance radiotherapy
toxicity, a potential delay of treatment in case of wound infection

70. Pregnancy-Preserving Management
Before 22 to 25 Weeks of Pregnancy
● If microscopic invasion after colposcopy is suspected, Diagnostic
conization is preferably performed at 12 to 20weeks of pregnancy.
● In Stage IA1, conization alone is a sufficient and relatively safe
treatment during pregnancy
● For higher stages of cervical cancer, Pelvic lymphadenectomy is
proposed to diagnose the high-risk disease (with positive nodes) that
may necessitate termination of pregnancy and application of
standard treatment.

72. After 22 to 25 Weeks of Pregnancy
● A complete pelvic and/or paraaortic lymphadenectomy is difficult
to perform
Therefore,Decision making cannot rely on the nodal status.
● In stage IA2 and IB1 tumors smaller than 2 cm, Delay of treatment
until fetal maturity, with delivery
● When progressive disease is observed, early delivery or NACT is
advocated.
● Alternatively, NACT can be started straight away. For higher
stages,NACT is the only way to preserve pregnancy and reach fetal maturity.

73. Radiotherapy Delivery
● Cancers which are remote from the pelvis usually can be
adequately treated with radiotherapy, based on careful
planning.
● Not the case for cancers located in the pelvis, which
cannot be irradiated without severe or, more probably,
lethal consequences for the foetus.

74. During Radiotherapy Treatment
● Radiotherapy to non-pelvic fields during pregnancy can be
performed, but it requires careful estimation of fetal dose and may
require additional shielding.
● Important factor in fetal dose: Distance from the edge of the radiation
field. The dose decreases approximately exponentially with distance.
● Fetal doses below 100 mGy should not be considered a reason
for terminating a pregnancy.
● Additional shielding can reduce the fetal dose by 50%.
● If fetal dose is above 50–100 mGy, a shield may be constructed with
4–5 half-value layers of lead.
● Measure dose to the fetus in a phantom for simulated treatment with
the shielding in place, adjusting radiation amount and location.

75. ● Monitor the fetal size and growth throughout the course of treatment
and reassess fetal dose if necessary.
● At completion of treatment, document total dose including range of
dose to the fetus during therapy.
● The radiation risk for fatal cancer is conservatively assumed to be
0.6% per 100 mGy fetal dose.
● Decreased IQ and possible retardation are only detectable when
fetal doses >100 mGy during the 8th to 25th weeks of gestation
● If the fetal absorbed dose is high, for example, in excess of 500 mGy,
and it was absorbed during the 3rd to 16th weeks after conception,
there is a substantial chance of growth retardation and central nervous
system damage

76. Pregnancy termination
• Early-stage disease: Radical hysterectomy with the fetus in situ
and with preservation of the ovaries whenever possible.
• Advanced disease: Definitive treatment should be administered
as in the nonpregnant patient.
• Before chemoradiation: Evacuate the uterus, esp if the fetus >20
weeks of gestation.
• If termination is not performed before chemoradiation and
treatment does not result in spontaneous abortion:
Medical/surgical uterine evacuation after chemoradiation

77. Malignant Melanoma
Incidence:
● The real incidence of melanomas during pregnancy is unknown
● The estimated incidence of melanomas in pregnancy is from 2.8 – 5
● cases / 100,000 pregnancies
● Swedish Cancer Registry 1973-1984: Melanoma was the most
● Common tumour of pregnant women (25% of total)

78. ● The diagnosis of melanoma is always made by tumor excision
and pathological examination.
● Tumor thickness, primarily, as well as tumor site remain
important prognostic factors for pregnant women with
melanoma.
● The effect of pregnancy on tumor location and thickness is still
unclear
● Diagnosis: Excisional biopsy safe

79. Management:
● Wide local excision with 1-2 cm margins under general or regional
anaesthesia
● Stage I-II: LND or SLNB (avoid the methylene blue dye) probably
safe. Survival benefit has not been proven (MSLT-1 trial)
● Stage III-IV: Therapeutic lymph node dissection should be
performed, as well as resection of satellite, in-transit or isolated
metastases

80. Effect of pregnancy on melanoma
● Mortality 50%
● 5 controlled studies failed to show inferior survival of pregnant
women with melanoma compared to matched non-pregnant
patients
● 10-year OS of 85% vs. 82% for >500 pregnant women vs. 5000
non-pregnant women with melanoma
● Pack GT and Scharnagel IM. Cancer 1951;4(2):324-334;
● 2. Lens MB et al. J Clin Oncol 2004;22(21):4369-4375

81. Ovarian Cancer
● Incidence : 4-5 / 100,000
● 2-5% of pregnancies are complicated by ovarian mass (25,000 pt)
● 90% of cases regress spontaneously till 12th week of pregnancy
● Ovarian malignancy is usually diagnosed at early stage (60-80% in
stage I) - Ultrasound
Histopathology:
● 50-60% epithelial tumours
● 25-40% germ cell tumours
● 5-10% sex cord tumours

82. Management
IA, G1 / borderline :
● Adnexectomy, omentectomy, peritoneal washings
● Post-delivery restaging
IA, G2, G3, IB, IC, IIA :
● Lymphadenectomy (till 20th week of pregnancy)
● Postpone lymphadenectomy and radical surgery after delivery
● Adjuvant chemotherapy
IIB and higher:
● Radical surgery + termination of pregnancy
● Cytoreductive surgery + chemotherapy + surgery during pregnancy
Cytoreductive surgery + chemotherapy during pregnancy + restaging after delivery
Tewari K et al. Gynecol Oncol 1997;66(3):531-534; Machado F et al. Gynecol Oncol 2007;105(2):446-450; Picone O et al. Gynecol Oncol
2004;94(2):600-604

83. Neoadjuvant / adjuvant chemotherapy:
● Epithelial ovarian tumours
− Paclitaxel 175 mg/m2 + carboplatin 6 AUC
− Paclitaxel 175 mg/m2 + cisplatin 75 mg/m2
● Non-epithelial ovarian tumours
− 1st choice: Paclitaxel + carboplatin
− 2nd choice: Bleomycin, etoposide ?, Cisplatin1
− Alternative: Cisplatin + bleomycin

84. Prognosis
● Similar prognosis to non-pregnant population (histology and
stage)
● Prognosis is quite favourable since most ovarian cancers are of
low grade and stage
● 5-year survival rate: 60-75%

85. GI malignancies associated with
pregnancy
● Colorectal cancer: 350 cases reported
● Gastric cancer: Very rare, 150 cases reported
● Pancreatic cancer: Exceedingly rare
● Hepatoma: Exceedingly rare, 45 cases reported
● GI cancers in pregnancy
Management of localized colorectal cancer after first 24 weeks of gestation:
● Watch-and-wait till delivery in week 32-34 and surgery
● Pregnancy termination and surgery
● Attempt surgery and continuation of pregnancy
● RT only possible after pregnancy termination or post partum

86. Advanced stage
● Termination of pregnancy and chemotherapy during 1st trimester
● Chemotherapy in 2nd and 3rd trimesters safe.
● Only case reports on bevacizumab, cetuximab, erlotinib,
oxaliplatin
● Pre-eclampsia is caused by high levels of VEGF inhibitors

87. Lymphomas
● Hodgkin lymphoma : 1 :1,000 – 1: 3,000 deliveries
● Non- Hodgkin lymphoma : 1: 5,000 deliveries
● To avoid teratogenicity, a limited staging work-up for
● Hodgkin’s disease and NHL is mandatory during pregnancy.
● Staging should always include physical examination, blood
tests, chest x-ray, bone marrow biopsy, and abdominal
ultrasound.
● Tomographic and isotope scans are contraindicated

88. Treatment
● During 1st trimester pregnancy termination might be considered
because of higher risk of congenital anomalies
● Starting from 2nd trimester combination chemotherapy is feasible
and safe
● Patients close to term are good candidates to delivery anticipation

90. NHL
● Watchful waiting is safe in most indolent lymphoma patients
(low grade follicular lymphoma, marginal zone lymphoma, lymphocytic
lymphoma)
But most pregnant patients with non-Hodgkin lymphomas have
aggressive histology !
● High rate of Burkitt‘s lymphoma with poor outcome
● High incidence of breast, uterine, cervical and ovarian involvement

92. ● There seems to be no evidence for teratogenic effect of
local treatment with supradiaphragmatic radiotherapy,
especially in early trimesters, or chemotherapy, mainly
given during the 2nd or 3rd trimester of pregnancy.

93. Leukemia during pregnancy
● It is estimated to range from 1 in 75,000 to 100,000
pregnancies .
● Acute leukemias are more frequent.
● Among them, acute myeloid leukemia is diagnosed twice as
often as lymphatic leukemia.
● Concerning chronic leukemias, chronic myeloid leukemia (CML)
accounts for less than 10% of all cases.
● Chronic lymphocytic leukemia is very rare since it is a
malignancy most commonly detected in the elderly.

94. Treatment
● During 1st trimester pregnancy termination might be considered
because of higher risk of congenital anomalies
● Starting from 2nd trimester combination chemotherapy is
feasible, with some caveats
● Patients close to term are good candidates to delivery
anticipation

95. ● The therapeutic management of pregnant women with acute
leukemia is very difficult and the final decisions should be made by
the hematologist/oncologist, the patient, and the family.
● Abortion should be recommended during the 1st trimester of
pregnancy, however, if the patient expresses the desire to keep the
baby, then nonteratogenic cytostatics should be used.
● Systemic chemotherapy during later trimesters is not associated with
teratogenic risk

96. ● CML is usually treated conservatively.
● The successful administration of Hydroxyurea and Interferon or
even of leukapheresis has been reported in single cases.
● If the option for aggressive treatment (i.e., bone marrow
transplantation) has been taken, then this should be delayed
until after delivery.

97. ● Imatinib during 1st trimester has a considerable risk of
congenital anomalies and spontaneous abortion
● Several uneventful pregnancies reported
● Interferon-alpha can be safely administered throughout the
course of pregnancy
● ?? Shift from Imatinib to IFN (or nothing) before conceiving

98. METASTASES OF MATERNAL TUMORS TO
THE
PLACENTA & FETUS
● Vertical transmission of cancer is exceptionally rare, although maternal cells
do reach the fetus.
● From 1866 to 1999, 58 cases of documented maternal malignancy metastatic to the placenta and
fetus were reported in the western literature
● The tumors most commonly seen coexisting with pregnancy are not those
most commonly found involving the products of conception (placenta and
fetus).
● The most likely way for dissemination is through the hematogenous route.The
rarity of this dissemination is probably due to the placental barrier and the fetal
immune system.
● The most common tumor metastasizing to the placenta or fetus is Malignant
melanoma, accounting for 30% of all pregnancy- associated tumors. The
second most frequent malignancies are leukemia and lymphoma followed by
carcinoma of the breast and lung

99. Recommendations
● The placenta should be submitted to macroscopic and histopathologic
examination
● Cytologic examination should be performed in both maternal and umbilical
cord blood
● Neonates should be clinically examined for palpable skin lesions,
organomegaly or other masses.
● Follow-up of the healthy baby every 6months-2years with physical
examination, chest xray and liver function tests.
● If metastases are found in both the placenta and the embryo, especially in
melanomas, further IHC, karyotypic and cytogenetic studies as well as HLA
typing contribute to the accurate identification of the malignant clone

100. THERAPEUTIC ABORTION IN
PREGNANT WOMEN WITH CANCER

101. ● It becomes more important when the diagnosis of cancer is made
● For the1st trimester, the most important parameters for consideration
are:
− the stage of the disease;
− the need to provide chemotherapy,
− the potential curability of this disease
● Absence of guidelines

102. ● Therapeutic abortion during the 1st trimester of pregnancy could be
recommended primarily
− for Locally advanced-stage Cervical carcinoma,
− Advanced breast cancer or breast cancer necessitating
adjuvant systemic treatment,
− Stage III-IV aggressive NHL or Hodgkin’s disease
− Acute leukemia.
− any other chemosensitive or nonchemosensitive solid tumor
*Provided that the decision follows a thorough discussion among the
pregnant patient, the doctor, and the family
● Considered that abortion is not a therapeutic procedure in these
cases but termination of pregnancy can be considered in order to
facilitate completion of treatment.(Berry et al. 1999)

103. THANK YOU