Cancer management during pregnancy - ESMO
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Cancer management during
pregnancy
Stergios Boussios, George Pentheroudakis, Nicholas Pavlidis,
MD MD PhD MD, PhD, FRCP (Edin)
Resident in Medical Assistant Professor of Oncology Professor in Medical Oncology
Oncology Medical School School of Medicine,
Medical School University of Ioannina, University of Ioannina,
University of Ioannina, Greece Greece
GreeceAn important topic… 1. Involves two people, the mother and the foetus 2. Should aim for optimal maternal treatment and safeguard foetal well-being (when the two are compatible!) 3. Trend for delaying pregnancy into the later reproductive years: expected to see more cases of cancer complicating pregnancy 4. Medical, ethical, psychological and religious issues
“Optimal Gold Standards” 1. To try to benefit mother’s life 2. To try to treat curable malignant disease of pregnant women 3. To try to protect foetus and new-born from harmful effects of cancer treatment 4. To try to retain mother’s reproductive system for future gestations
Occurrence of cancer in pregnancy Cancer is the 2nd most common cause of death during the reproductive years The occurrence of cancer in a pregnant woman is relatively rare (0.07 - 0.1% of all malignant tumours) In Europe, yearly 3,000 to 5,000 patients are diagnosed with cancer during pregnancy Annually in USA there are 3,500 cases (about 1 case every 1,000 pregnancies)
Epidemiology
Incidence of malignant tumours during gestation
Tumour type Incidence*
Breast cancer 1:3,000-10,000
Cervical cancer 1.2:10,000
Hodgkin’s disease 1:1,000-6,000
Melanoma 2.6:1,000
Leukaemia's 1:75,000-100,000
Ovarian cancer 1:10,000-100,000
Colorectal cancer 1:13,000
*Malignant tumours per pregnancies or deliveries
Pavlidis N. Oncologist 2002;7(4):279-287Chemotherapy safety
When a drug is
administered to the
mother, placental
transfer of the drug
could be hazardous
to the foetus
Reprinted from Cardonick E et al. Lancet Oncol 2004;5(5):283-291, with permission from ElsevierChemotherapy safety Reprinted from Cardonick E et al. Lancet Oncol 2004;5(5):283-291, with permission from Elsevier
Chemotherapy during pregnancy Most drugs with MW
Effects of chemotherapy by
gestational stage
Stage Effect
1st trimester Abortion 20-30%
Malformations 10-25%
2nd and 3rd trimesters IUGR, low birth weight, miscarriage,
premature birth 20-40%
Perinatal period Maternal/foetal myelosuppression,
infections, haemorrhage
Late effects No detrimental effects on physical and
neurocognitive function, gonads or
second tumours
IUGR = intrauterine growth restrictionPotential for abortion/malformations by
drug type
High Low Unknown
Aminopterin 5FU Taxanes
Methotrexate Doxorubicin Platinum compounds
Chlorambucil Daunorubicin Rituximab
Busulfan Vinca alkaloids Imatinib
Cyclophosphamide Interferon Trastuzumab
Mustard Other mAbs
Procarbazine
Ara-C
Tamoxifen
Cardonick E et al. Lancet Oncol 2004;5(5):283-291Long-term follow-up of people exposed to
chemotherapy in utero
Aviles et al. 2001: FU of 84 children for a median of 19 years
Normal physical, neurological, psychological development
Normal sexual development-12 became parents
No increased risk for second tumours
Nulman et al. 2001: Summary of 111 children followed up for 2-19
years
Normal physical
Normal neurological development
Avilés A et al. Clin Lymphoma 2001;2(3):173-177;
Nulman I et al. Br J Cancer 2001;85(11):1611-1618. ReviewSupportive care
Hormonal therapy
Ondansentron + metoclopramide:
Safe during pregnancy (most accumulated data and two prospective
RCTs)
Erythropoietin:
Not crossing placenta
No reported teratogenic effects
Transfusions preferable?
GCSF:
Crosses the placenta
No teratogenesis in rats or humans
Use only in absolute need for protracted febrile neutropenia
Biphosphonates:
Not recommended bone and renal malformations in animalsBiological effects of ionising radiation Deterministic effects: Biological effects due to severe cellular damage Characterised by a «threshold dose» and by severity that increases with absorbed dose Abortion, stillbirth, congenital malformations, mental retardation, IUGR, low birth weight Stochastic effects: Biological effects due to radiation-induced modifications of cells (mutations) No safe «threshold dose» exists According to the Linear - No Threshold Model, the probability of appearance of stochastic effects diminishes with lower absorbed doses, though the severity does not Second cancers during childhood or adult life
Safety of radiodiagnostic procedures:
Stochastic effects
Stewart et al. 1956
Mac Mahon et al. 1962
In utero exposure to radiodiagnostic procedures has an increased risk
(1.3 - 3.0) of leukaemia or solid tumours, especially when exposure was
during the 1st trimester
Helmrot et al. 2007
No increased risk of leukaemia or second tumours in 652 children
irradiated with diagnostic x-ray in utero
Absolute risk for entire life span: 0.015%/mGy
Stewart et al. 1956;
MacMahon B et al. J Natl Cancer Inst 1962;28(5):1173-1191;
Helmrot E et al. Eur Radiol 2007;17(1):205-209Radiation dose guidelines:
Deterministic effects
Dose Foetus effect
Up to 100 mGy No major effect
>100 to 200 mGy Increased risk
>2000 mGy Malformations in most or abortion
Absorbed dose: 1 Gy = 1 Joule/Kg = 100 cGy or rad
Equivalent dose: 1 Sv = 1 Gy x WrAdverse effects of radiation in relation to gestational stages
Recommended staging imaging tests in
pregnant women with cancer
Should be 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 (lead apron) and abdominal ultrasound can be indicated
and are safe
Nicklas et al. , Semin Oncol 2000;27:623:
Gadolinium crosses the placenta and causes foetal abnormalities in
rats, MRI causes heating/cavitation in early embryos
Nicklas AH and Baker ME. Semin Oncol 2000;27(6):623-632Breast cancer associated with pregnancy
(1)
INCIDENCE
Approximately 1:3,000-10,000 pregnancies (the most common)
3% of all breast cancer is associated with pregnancy
Pregnancy-associated breast cancer is defined as cancer that is
diagnosed during pregnancy or within 1 year postpartum
Median age: 33 years (23-47)Breast cancer associated with pregnancy
(2)
DIAGNOSIS
Mammography sensitivity: 68% (due to increased density and
congestion)
Ultrasonography sensitivity: 93%
FNA, Open or Core Needle breast biopsy confirms diagnosis
Pregnant women have a 2.5 - fold higher risk to present with
advanced diseaseBreast cancer features in pregnant
women (3)
1. Invasive ductal
2. Grade 2-3 60-80%
Similar to all non-pregnant
3. Lymph node involvement 40-75% women with breast cancerBreast cancer associated with pregnancy
(4)
MD Anderson (57) IEO (20)
Hahn K et al. Peccatori F et al.
Cancer 2006 Breast Ca Res Treat 2009
FAC Regimen Weekly epirubicin
37 W Gestational age at delivery 35 W
2/57 (4%) Pre-term pregnancies 1/20 (5%)
3/57 (5.3%) Congenital anomalies 1/20 (5%)
Maternal outcome at 38m
70% DFS 70%
77% OS 85%
Hahn KM et al. Cancer 2006;107:1219-1226;
Peccatori FA et al. Breast Cancer Res Treat 2009;115(3):591-594Breast cancer associated with pregnancy
(5)
Treatment of cancer during pregnancy: the need for tailored
strategies*
Why weekly?
Allow close monitoring of pregnancy
Low peak plasma concentration resulting in
Lower toxicity (more safe)1
Possible lower placental transfer & foetal exposure2
Easy interruption in case of toxicity
Efficacy of weekly regimens is established outside pregnancy3
*Azim HA and Peccatori FA. J Clin Oncol 2010;28(18):e302-e303;
1. Norton L et al. Oncologist 2005;10(6):370-381;
2. Zucchetti M. Personal communication;
3. Ellis MJ et al. J Clin Oncol 2011;29(17):2342-2349Breast cancer associated with pregnancy
(6)
European Registry on BC during pregnancy
Total number of patients 315
Treated with chemotherpay 121 (51%)
Treated with anthracycline-based regimens 95 (78%)
AC/EC 71
FEC 20
Single agent epirubicin/doxorubicin 4
Foetal outcome (chemo vs. no chemo)
Median birth weight at delivery: 2760 gm (vs. 2810)
Median gestational age at delivery: W37 (vs. W38)
Median HB level post-partum: 16 g/dl
Loibl S et al. Proc SABCS 2010;Abstract S6-S2Breast cancer associated with pregnancy
(7)
Long-term effects of in utero exposure to doxorubicin-based regimens
Median FU Number Late effects
Doxorubicin-based
regimens
18 Y 89 None
(leukemia/lymphoma)
FAC (CI Doxo) 6Y 18 None
Avilés A et al. Ann Oncol 2006;17(2):286-288;
Hahn KM et al. Cancer 2006;107:1219-1226Breast cancer associated with pregnancy
(8)
Long-term effects of in utero exposure to weekly epirubicin (n=30)
Age 0-1 Age 2-3 Age 4-5 Age 6-7 Age 8
No 5 10 9 3 3
Normal development!
Updated Peccatori F et al. Breast Cancer Res Treat 2009;115(3):591-594Breast cancer associated with pregnancy
(9)
Taxanes in gestational breast cancer
Number
Breast cancer 27
Other 13
Regimen
Paclitaxel 21
Docetaxel 16
Both 3
Neonatal outcome
Gestational age at delivery W 36
Foetal weight 2400 g
Median FU 18 m No anomalies reported
Mir O et al. Ann Oncol 2010;21(2):425-426Breast cancer associated with pregnancy
(10)
Transplacental transfer of chemotherapy in baboon models
Van Calsteren V et al. Gynecol Oncol 2010;119:594-600;
Van Calsteren V et al. Int J Gynecol Cancer 2010;20:1456-1464Breast cancer associated with pregnancy
(11)
CMF in pregnancy
CMF: Normal outcome in 2nd, 3rd trimester exposure (25 cases)1
AVOID during PREGNANCY 1st trimester
CMF < “Anthracyclines” < “Anthra + Taxanes”2
MTX used in induction of abortion3
1st trimester exposure = highly teratogenic4
1. Azim HA Jr et al: Cancer Treat Rev 2010;36(2):101-109;
2. Bedard PL and Cardoso F. Ann Oncol 2008;19(suppl 5):v122-v127;
3. Say L et al. Cochrane Database Syst Rev 2005;(1):CD003037;
4. Aebi S and Loibl L. Recent Results Cancer Res 2008;178:45-55. ReviewBreast cancer associated with pregnancy
(12)
HER2 plays a pivotal role in the development
of different foetal organs
LUNG KIDNEY INTESTINE SKIN
Patel NV et al. Am J Respirol Mol Biol 2000;22(4):432-440; Courtesy of Kokai Y et al. Proc Natl Acad Sci U S A 1987;84(23):8498-8501Breast cancer associated with pregnancy
(13)
TRASTUZUMAB IN GESTATIONAL BREAST CANCER
Number of cases (2005-2011) 17
Setting
In combination with Chemotherapy Hormonal therapy Alone
4 2 11
Time Preconception to 3rd trimester
Pregnancy
Anhydramnios 10/17 (59%)
Ectopic pregnancy/abortion 2/17 (12%)
PROM 1/17 (6%)
IUGR 1/17 (6%)
Baby
Respiratory failure 6/17 (35%)
Renal failure 3/17 (18%)
Death 4/17 (23,5%)
Premature 1/17 (6%)
IUGR = intrauterine growth restriction, PRO = premature rupture membranesBreast cancer associated with pregnancy
(14)
Trastuzumab and the amniotic fluid
Anhydramnios
Trastuzumab blocks HER-2 expressed in foetal kidney
It interferes with VEGF signalling responsible for amniotic fluid
production and reabsorption
Sekar R and Stone PR. Obstet Gynacol 2007;110(2 Pt 2):507-510;
Pant S et al. J Clin Oncol 2008;26(9):1567-1569Breast cancer associated with pregnancy
(15)
Facts about tamoxifen
Pregnancy is possible on tamoxifen
Moreover, currently used in induction of ovulation and licensed in
the UK for managing infertility
Preclinical models have shown that it causes ambiguous genitalia
and ++ genital cancers in off springs
Barthelmes L and Gateley CA. Breast 2004;13(6):446-51. ReviewBreast cancer associated with pregnancy
(16)
Biphosphonates
Concerns
Preclinical models: Skeletal deformities, genital defects
Maternal hypocalcaemia: Affects uterine contraction
However
A systematic review of literature till 09-2008
52 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):505-507Breast cancer associated with pregnancy
(17)
Recommendations of an international consensus meeting
Diagnosis of breast cancer in pregnancy
Near term (37 weeks)* Before term (before 37 weeks)
Delivery at ≥37 weeks
Staging and treatment
Surgery:
Breast conserving surgery or mastectomy
Sentinel procedure or axillary dissection
(Neo-) Adjuvant chemotherapy
From 14 weeks on
Currently used cytotoxic drugs are allowed
Amant F et al. Eur J Cancer 2010;46(18):3158-3168Breast cancer associated with pregnancy
(18)
Number 12
Median age (range) 38 (33-42)
Clinical stage T1N0 (7); T2N0 (5)
Median gestational age at SLN 17w (5-33w)
(range)
SLN outcome 10 –ve; 2 +ve
At 32 months of FU
• Patient No axillary recurrence
• Babies Normal development
Gentilini O et al. Eur J Nucl Med Mol Imaging 2010;37:78-83Breast cancer associated with pregnancy
(19)
Recommendations of an Diagnosis of breast cancer in pregnancy
international consensus meeting
Near term (37 weeks)* Before term
(before 37 weeks)
“…The Panel encountered scarce Delivery at ≥37 weeks
literature data on the outcome of
children whose mothers were given
Staging and treatment
therapeutic irradiation during BCP…”
“…However, based on data on long Surgery:
term outcome of pregnant atomic bomb Breast conserving surgery or mastectomy
survivors and based on theoretical Sentinel procedure or axillary dissection
assumptions, the Panel accepts (Neo-) Adjuvant chemotherapy
radiotherapy as a relatively safe From 14 weeks on
treatment option during the first and Currently used cytotoxic drugs are allowed
second trimester of pregnancy.
The Panel states that better clinical No chemotherapy after 35 weeks
data are needed” Schedule delivery ≥37 weeks
Chemo-delivery interval of 3 weeks
Amant F et al. Eur J Cancer 2010;46(18):3158-3168Breast cancer associated with pregnancy
(20)
Do patients with GBC have worse prognosis compared
to matched controls ?
Around 30 published case-control trials with conflicting results!
Limitations:
Small-sized (lack of power)
Multi-institutional
Lack of matching according to stage – therapy
Scarce information regarding pathological featuresBreast cancer associated with pregnancy
(21)
Unpublished dataRecent studies… (1)
Prognosis of Women With Primary Breast Cancer Diagnosed During
Pregnancy: Results From an International Collaborative Study
Two international multicenter cohort studies collaborated in this initiative
Aim of the study Estimation of the prognostic impact of pregnancy when
breast cancer is diagnosed
Results
447 women with BCP registered, of whom 311 were eligible for this analysis.
240 (77.2%) of 311 patients were included prospectively
These 311 patients were compared with 865 women with breast cancer who were not
pregnant (ratio 1:2.78)
The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19
(95% CI, 0.73 to 1.93; P = .51) for OS
Treatment
Pregnant patients Administration of taxanes to 95 (47.03%) with adjuvant chemotherapy
and to 69 (71.13%) with neoadjuvant chemotherapy
Nonpregnant patients Administration of taxanes to 168 (30.88%) with adjuvant
chemotherapy and to 79 (77.45%) with neoadjuvant chemotherapy
Conclusion
Similar survival for patients between pregnant and non pregnant patients with breast cancer
Amant F et al. J Clin Oncol 2013;31(20):2532-2539Recent studies… (2)
Prognosis of Pregnancy-associated Breast Cancer: A Meta-analysis of 30
Studies
Comprehensive analysis of all published studies that addressed the
prognosis of pregnancy-associated breast cancer
The primary and secondary end-points were overall and disease-free
survival
Overall survival
Significantly worse OS compared to breast cancer controls (pHR: 1.44; 95% CI [1.27–1.63])
Disease free survival
Significant risk of relapse compared to controls (pHR: 1.60; 95% CI [1.19–2.16])
Conclusions
1. Poorer prognosis because diagnosis is delayed in new mothers
2. Pregnancy has an independent effect on prognosis via influencing the biology of breast
cancer
3. Breast cancer arising postpartum was significantly associated with poor OS
4. The trend was not as substantial in patients diagnosed during pregnancy
5. Poorer overall survival is particularly obvious in patients diagnosed in the 1-year
post-partum period than those diagnosed during pregnancy
Azim HA Jr et al. Cancer Treat Rev 2012;38(7):834-842Recent studies… (3)
Treatment of Breast Cancer During Pregnancy: An Observational Study.
447 patients were registered, 413 of whom had early breast cancer
Primary endpoint foetal health for up to 4 weeks after delivery
Birth weight was affected by chemotherapy exposure after adjustment for
gestational age (p=0.018), but not by number of chemotherapy cycles
(p=0.71)
40 (10%) of 386 infants had side-effects, malformations, or new-born
complications
More common in infants born before the 37th week of gestation (p=0.0002)
Adverse events were more common in those who received chemotherapy in utero
compared with those who were not exposed (p=0.00045)
Median disease-free survival for women with early breast cancer
70.6 months in women starting chemotherapy during pregnancy
94.4 months in women starting chemotherapy after delivery
Delay of cancer treatment did not significantly affect disease-free survival
for mothers with early breast cancer
Preterm birth was strongly associated with adverse events.
Loibl S et al. Lancet Oncol 2012;13(9):887-896Breast cancer associated with pregnancy
(25)
Elective systemic therapy in pregnancy: Summary
Consider
weekly
applicationBreast cancer associated with pregnancy
(26)
How safe is pregnancy after breast cancer?
No. of RR of Practical guidelines
Author Year
cases death
(despite controversies)
Ives 2006 123 0.59
Patients with early stage
Blakely 2004 47 0.71 disease (stage I-II), a delay of
Mueller 2003 438 0.54 at least 2 years is necessary
Vellentgas 1999 53 0.80 Patients with stage III should
be deferring pregnancy for at
Kroman 2008 465 0.73
least 5-years
Von Schoulz 1995 50 0.48
Patients with stage IV should
Sankila 1994 91 0.20 not consider conception at allPregnancy safety after breast cancer (27)
Practical guidelines
(despite controversies) Time to pregnancy RR of death
Patients with early stage
disease (stage I-II), a delay of 2-3 years 0.49
at least 2 years is necessary
Patients with stage III should 3-4 years 0.30
be deferring pregnancy for at
least 5-years
4-5 years 0.19
Patients with stage IV should
not consider conception at all
Mueller BA et al. Cancer 2003;98(6):1131-1140Conclusions
Treatment during pregnancy is feasible, but
It is safe to consider pregnancy in women with history of
successfully treated BC. According to our results, counselling
against pregnancy in these patients is not justified
Caution should be made as the data used for analysis is not
individual patient data, but rather, abstracted data
“Though the narrowness of today might reassure us that an
intervention is safe, it is only with the wisdom of time that the full
consequences of our actions are revealed”
Goodman A. New Engl J Med 2010;362(11):e37Cervical carcinoma associated with
pregnancy (1)
Incidence
One of the most common malignancy during pregnancy
(1: 1,000-10,000)
Incidence varies from 0.02% - 0.9%
The incidence recently declines due to effective screening
Diagnosis
Pregnant women have a 3.1- fold higher chance of early detection
(stage I) due to frequent obstetrical examinations
Colposcopy and colposcopy-directed biopsy can be safely
performed in women with abnormal Pap smearCervical carcinoma associated with
pregnancy (2)
STAGE 0 (CIN)
Conservative management
Use colposcopy every 6-8 weeks (or colposcopical bx)
Delay treatment postpartum
25% of lesions can regress spontaneously
Avoid cone bx or conisation. Abortion rates 17%
Avoid conisation. Abortion rate 33%Cervical carcinoma associated with
pregnancy (3)
Management – pregnancy preserving
SURGERY – literature
IA1
Conisation1
IA2
Simple trachelectomy + lymphadenectomy2
IB1, IB2
Conisation + lymphadenectomy3,4
Vaginal radical trachelectomy + lymphadenectomy5,6
Abdominal radical trachelectomy + lymphadenectomy7-9
With permission of Pavlidis N. ESMO 2012;
1. Robova H et al. Eur J Gynecol Oncol 2005;26(6):611-614;
2. Ben-Arie A et al. Obstet Gynecol 2004;104(5 Pt 2):1129-1131;
3. Van Calsteren K et al. Acta Obstet Gynecol Scand 2008;87(2):250-253;
4. Marnitz S et al. Fertil Sterili 2009;92(5):1748.e1-e4; Herod, JJO, IJOG, 2010, own case;
5. van de Nieuwenhof HP et al. Int J Gynecol Cancer 2008;18(6):1381-1385;
6. Iwami N et al. Int J Clin Oncol 2011;16(6):737-740;
7. Ungár L et al. Obstet Gynecol 2006;108(3 Pt 2):811-814;
8. Abu-Rustum N et al. Gynecol Oncol 2009;116(1):151-152;
9. Mandic A et al. Am J Obstet Gynecol 2009;201(2):e6-e8Cervical carcinoma associated with
pregnancy (4)
Management – pregnancy preserving
NEOADJUVANT CHEMOTHERAPY
IB1 (>2 cm), IB2
Postpone surgery/delivery
Regimen:1
Carboplatin 6 AUC + paclitaxel 175 mg/m2 every 3 weeks
Cisplatin 75 mg/m2 + paclitaxel 175 mg/m2 every 3 weeks
Other: Cytostatics, interval
Cisplatin 75 mg/m2 + doxorubicin 35 mg/m2 every 2 weeks *
Cisplatin 75 mg/m2 + paclitaxel 175 mg/m2 every 2 weeks *
Cisplatin 75 mg/m2 every 10 days
Cisplatin 50 mg/m2 + vincristine 1 mg/m2 every 3 weeks
With permission of Pavlidis N. ESMO 2012;
1. Amant F et al. Int J Gynecol Cancer 2009;19(suppl_1):S1-S12Cervical carcinoma associated with
pregnancy (5)
STAGE II, III, IV
Therapeutic abortion or watchful waiting (if 3rd trimester pregnancy)
If foetus viable preoperative caesarean section
Radical hysterectomy or Radiotherapy: treatments of choice
Neoadjuvant chemotherapy (buys time for waiting?)
Radical trachelectomy + laparoscopic LN dissection for fertility
preservation in selected patientsPrognosis of cervical carcinoma
associated with pregnancy (6)
No. of No difference in maternal
5-year
Investigator pregnant survival between pregnant and
OS
patients non-pregnant women1
Tarushim 28 72% More frequent local relapses in
women who had a vaginal
Van der delivery in comparison to those
44 80% who had caesarean section
Vange
(p=0.04)2
Sood 93 79% No difference found3
Jones 161 82%
1. Jones WB et al. Cancer 1996;77(8):1479-1488; Zemlickis D et al. 1991;9(11):1956-1961;
2. Sood AK et al. Obstet Gynecol 2000;95(6 Pt 1):832-838;
3. van der Vange N et al. Obstet Gynecol 1995;85(6):1022-1026Cervical carcinoma associated with
pregnancy (7)
Zemlickis D et al. J Clin Oncol 1991;9(11):1956-1961. Reprinted with permission. © (1991) American Society of Clinical Oncology.
All rights reservedOvarian cancer (1)
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 pregnancy1
Ovarian malignancy is usually diagnosed at early stage (60-80% in
stage I)
Ultrasound CA 125, AFP, HCG, CEA
Histopathology:
50-60% epithelial tumours
25-40% germ cell tumours
5-10% sex cord tumours
1. Giuntoli RL 2nd et al. Clin Obstet Gynecol 2006;49(3):492-505; Bernhard LM et al. Obstet Gynecol 1999;93(4):585-589Ovarian cancer-management (2)
IA, G1 / borderline tumours
Adnexectomy, omentectomy, peritoneal washings, bs
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 pregnancy1
Cytoreductive surgery + chemotherapy + surgery during pregnancy2
Cytoreductive surgery + chemotherapy during pregnancy + restaging
after delivery3
1. TewariK et al. Gynecol Oncol 1997;66(3):531-534;
2. Machado F et al. Gynecol Oncol 2007;105(2):446-450;
3. Picone O et al. Gynecol Oncol 2004;94(2):600-604Ovarian cancer-management (3)
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
1. Amant F et al. Int J Gynecol Cancer 2009;19(suppl_1):S1-S12Ovarian cancer (4) Prognosis Similar prognosis to non-pregnant population (histology and stage matched) Prognosis is quite favourable since most ovarian cancers are of low grade and stage 5-year survival rate: 60-75%
Melanoma associated with pregnancy (1)
30 – 35% of melanomas in women occur during child-bearing years
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)
Superficial spreading and nodular melanomas1
Diagnosis: Excisional biopsy safe
1. Lens MB and Dawes M. Br J Dermatol 2004;150(2):179-185Melanoma associated with pregnancy (2) Management Wide local excision with 1-2 cm margins under general or regional anaesthesia Stage I-II: ELND 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
Melanoma associated with pregnancy (3)
Effect of pregnancy on melanoma
Mortality 50%!1
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 melanoma2
1. Pack GT and Scharnagel IM. Cancer 1951;4(2):324-334;
2. Lens MB et al. J Clin Oncol 2004;22(21):4369-4375GI malignancies associated with
pregnancy (1)
GI cancers in pregnancy
Colorectal cancer: 350 cases reported
Gastric cancer: Very rare, 150 cases reported
Pancreatic cancer: Exceedingly rare
Hepatoma: Exceedingly rare, 45 cases reported
Management of localized colorectal cancer
after first 24 weeks of gestation
Watch-and-wait till delivery in week 32-34 and surgery
OR
Pregnancy termination and surgery
OR
Attempt surgery and continuation of pregnancy
RT only possible after pregnancy termination or post partumGI malignancies associated with
pregnancy (2)
Advanced disease
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 inhibitorsLymphoma associated with pregnancy (1)
Hodgkin lymphoma : 1 :1,000 – 1: 3,000 deliveries
Non- Hodgkin lymphoma : 1: 5,000 deliveries
Hodgkin lymphoma during pregnancy: Treatment
Is immediate treatment necessary?
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 anticipationLymphoma associated with pregnancy (2) With permission of Pentheroudakis G. ESMO 2008
Systemic treatment of Hodgkin lymphoma
during pregnancy (3)
Azim HA Jr et al. Cancer Treat Rev 2010;36(2):101-109Prognosis of Hodgkin lymphoma during
pregnancy (4)
Does pregnancy affects prognosis?
In a review of 112 pregnancies among 374 women of childbearing
age with HL, pregnancy did not exacerbate HL and did not affect
the outcome1
A review of 21 pregnant women among 155 patients with HL
confirmed that survival is similar despite a slightly higher incidence
of advanced stage in pregnant patients2
1. Barry RM et al. Am J Obstet Gynecol 1962;84:445-454
2. Gobbi PG et al. Haematologica 1984;69(3):336-341Non-Hodgkin lymphoma during
pregnancy (5)
Different approaches according to pathology subtypes!
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 involvementSystemic treatment of non-Hodgkin
lymphoma during pregnancy (6)
Azim HA Jr et al. Cancer Treat Rev 2010;36(2):101-109Systemic treatment of non-Hodgkin
lymphoma during pregnancy (7)
Rituximab during pregnancy
Azim HA Jr et al. Expert Rev Clin Immunol 2010;6(6):821-826Leukemia during pregnancy:
Treatment (1)
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 anticipationALL and pregnancy (2)
Treatment and outcome
No patients (up to 2010) 21
Doxorubicin / Epirubicin 7
Daunorubicin – based 2
Drugs
Idarubicin – based 2
Others 10
Gestational age of 1st exposure 15 – 35 weeks
Gestational age at delivery 28 – 38 weeks
Premature 3
Foetal outcome
IUFD 2AML and pregnancy (3)
Treatment and outcome
No patients (up to 2010) 64
Drugs Cytarabine - based
Gestational age of 1st exposure 15 - 34 weeks
Gestational age at delivery 28 - 41
IUFD 4
IUGR 3
Premature 8
Foetal outcome Pancytopenia 3
Fetal distress 3
Maternal – fetal death 2
Congenital anomalies 5CML during pregnancy (4)
Imatinib during 1st trimester has a considerable risk of congenital
anomalies and spontaneous abortion
But
Several uneventful pregnancies reported
Interferon-alpha can be safely administered throughout the course
of pregnancy
Shift from Imatinib to IFN (or nothing) before conceiving?CML during pregnancy (5)
CML pregnant patients treated with imatinib
No patients / pregnancies 36/38
1st trimester stop after pregnancy: 23
1st trimester continued to 2nd or 3rd: 11
Time of 1st exposure
2nd trimester 2
3rd trimester 2
Spontaneous abortion 3
Pregnancy complications
Premature delivery 1
Hypospadias 2
Pyloric stenosis 1
Foetal adverse events
Meningocele 1
Post – natal foetal death 1
Less than 1 year 22
Normal fetal outcome
More than 1 year 11Breastfeeding
In general, all cytotoxic, hormonal
and targeted therapies are
contraindicated during
breastfeeding
Not recommended until at least 2-4
weeks after the completion of
chemotherapy
“Milk rejection sign”: Denial of
lactating infant to nurse from the
carcinomatous breast
Pentheroudakis G and Pavlidis N. Eur J Cancer 2006;42(2):126-140Placental – foetal metastasis Cases with foetal involvement by tumour type (out of 98 cases)
Incidence of placental involvement by
tumour type
Tumour type No. with
placental
involvement (%)
Melanoma 25 (28%)
Breast cancer 14 (16%)
Lung cancer 11 (12%)
Leukemias 10 (10%)
GI cancers 9 (10%)
Sarcomas 8 (9%)
Lymphomas 7 (8%)
Head-neck cancer 3 (3%)
Ovarian cancer 2 (2%)
CUP 2 (2%)
Cervical cancer 1 (1%)
Adrenal cancer 1 (1%)
Lakshminarayana P et al. J Med Case Rep 2007;1:21. © 2007 Lakshminarayana et al; licensee BioMed Central Ltd,
with permission under the Creative Commons Attribution LicenseRecommendations 1. The placenta should be submitted to macroscopic and histopathologic examination 2. Cytologic examination should be performed in both maternal and umbilical cord blood 3. Neonates should be clinically examined for palpable skin lesions, organomegaly or other masses. Follow-up of the healthy baby every six months for two years with physical examination, chest x- ray and liver function tests
Principles of systemic anticancer
treatment in pregnant women
The administration of systemic anticancer therapy
should follow certain important rules:
Medical oncologists should treat the pregnant mother and should
protect the foetus (if the two are compatible)
Systemic treatment is generally not allowed during the period of
organogenesis (1st trimester)
Systemic treatment (Chemotherapy) is safer to administer during
the 2nd and 3rd trimester of pregnancy, though increased rates of
some toxic effects should be discussed with the patient and family
Endocrine treatment should be avoided
No sufficient evidence is available on the safety/efficacy profile of
small-molecule inhibitors and monoclonal antibodies. They
should generally be withheldYou can also read
