Melanoma and Gastrointestinal cancer during pregnancy George Pentheroudakis Assistant Professor of Oncology Medical School, University of Ioannina Greece
Ob/Gyn: Oh No! She has cancer!
Med Onc: Oh No! She’s pregnant!
Surgeon/Primary Care: Oh No! She’s pregnant and has cancer!
DISTRIBUTION OF CANCER IN PREGNANT WOMEN Cancer 25:380, 1970
ADVERSE EFFECTS OF RADIATION IN RELATION TO GESTATION STAGES
RECOMMENDED STAGING IMAGING TESTS IN PREGNANT WOMEN WITH CANCER
Abdominal plain films, isotope scans, PET scans and CT-scans should be avoided .
Chest X-ray and abdominal ultrasound can be indicated and are safe.
Nicklas et al, Semin Oncol 2000;27:623: Gadolinium crosses the placenta and causes fetal abnormalities in rats, MRI causes heating/cavitation in early embryos.
EFFECTS OF CHEMOTHERAPY BY GESTATIONAL STAGE Maternal/fetal myelosup p ression, infections, hemorrhage. Perinatal period IUGR, low birth weight, premature birth 20- 3 0% 2 nd and 3 rd trimesters Abortion 20-30% Malformations 10-25% 1 st trimester E f f e c t S t a g e
Cohen-Kerem et al,
Ann Surg Oncol 2005
Mazzle et al,
Am J Obstet Gynecol
Surgery is effective and safe in pregnant women.
Highest risk of abortion (10%) with first-trimester or abdominopelvic operations.
Melanoma and pregnancy
1/3 of malignant melamonas in women occur during child-bearing years.
Swedish Cancer Registry 1973-1984: Melanoma was the most common tumour of pregnant women (25% of total).
Presentation: Mostly ABCD
Lens et al, 2004: Thicker tumours diagnosed.
Mostly superficial spreading and nodular melanomas.
Diagnosis: Excisional biopsy safe.
Wide local excision with 1-2 cm margins under general or regional anesthesia.
Stage I-II: ELND or SLNB 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.
Isosulfan blue or methylene blue not recommended during pregnancy.
Gentillini et al, Ann Oncol 2004;15:1348-
Keleher et al, Breast J 2004;10:492:
Tc99m-Sulfur colloid: Fetal dose probably <4 mGy.
Lyman et al, JCO 2005;23;7703:
Probably safe, not enough evidence for sensitivity and safety in pregnant women though.
Should be considered experimental.
Effect of pregnancy on melanoma
Pack et al, 1951: Mortality 50%!
5 controlled studies failed to show inferior survival of pregnant women with melanoma compared to matched non-pregnant patients.
Lens et al, 2004-Swedish Cohort Study: 10-year OS of 85% vs 82% for >500 pregnant women vs 5000 non-pregnant women with melanoma
Survival of pregnant vs non-pregnant age- stage-matched patients with melanoma; California Cancer Registry 1991-1999
Conclusion: Overall, the existing studies offer reassuring results concerning the risks of adverse birth outcome for women diagnosed with........before, during or shortly after pregnancy.
Hepatoma: Fatigue, ascites, nausea/vomiting, right upper quadrant pain and hypoglycemia
Colorectal cancer: Abdo/pelvic US, CXR, colonoscopy and biopsy, TRUS.
MRI without gadolinium in 1 st trimester.
Gastric cancer: US, transesophageal US, CXR, endoscopy with biopsy.
Pancreatic cancer: MRCP, US, CXR. ERCP with fluoroscopy not allowed in 1 st trimester.
Hepatoma: US, MRI.
Colorectal cancer during pregnancy
Management of localised disease during first 20-24 weeks
If possible, wait beyond first 8-12 weeks for abdominal surgery. SAB: 20% 3%
Don’t remove corpus luteum if possible until the 14th week (progesterone supp. 50mg BID)
Deliver at maturity (at around 34-36 weeks)
No proven teratogenic effects of anesthesia
Management of localised disease after first 24 weeks of gestation
Watch-and-wait till delivery in week 32-34 and surgery
pregnancy termination and surgery
attempt at surgery and continuation of pregnancy.
RT only possible after pregnancy termination or post partum
Termination of pregnancy and chemotherapy during 1 st trimester
Chemotherapy in 2 nd and 3 rd trimesters safe
Only case reports on bevacizumab, cetuximab, erlotinib, oxaliplatin
Pre-eclampsia is caused by high levels of VEGF inhibitors!
Emergency procedures and Abortion
An emergency laparotomy may be necessary upon occurrence of acute intestinal bleeding, perforation or obstruction
The indications for delivery by means of cesarean section are identical to those of the general population, with two additional ones:
- the presence of a bulky rectal cancer that compromises the birth canal
- the risk for extension of the perineotomy wound into a large anterior rectal carcinoma.
Overall survival of pregnant women with GI cancers is no different from that of general population patients with tumours of matched TNM stage, grade and number of involved lymph nodes.
Delayed diagnosis seems to be the most probable cause of pregnant patient presentation with advanced stage, high volume disease, while aggressive disease behaviour in young ages may be a minor contributor.
INCIDENCE OF INVOLVEMENT OF PRODUCTS OF CONCEPTION BY TUMOUR TYPE (out of 98 cases) 28 (28.5%) Melanoma N o of CASES (%) TUMOUR TYPE 14 (14%) Breast cancer 10 (10%) Leukemias 13 (13%) Lung cancer 9 (9%) GI cancers 8 (8%) Sarcomas 7 (7%) Lymphomas 3 (3%) Head-neck cancer 2 (2%) Ovarian cancer 2 (2%) CUP 1 (1%) Cervical cancer 1 (1%) Adrenal cancer
Sections of placenta show multiple aggregates of atypical epithelioid cells in the intervillous space. (Hematoxylin-eosin stain; original magnification X 100)
A MELANOMA CASE
RECOMMENDATIONS FOR THERAPEUTIC ABORTION
Whenever treatment should be given during 1 st trimester:.
Advanced malignancy and poor life expectancy .
Non-early stages of cervical , ovarian cancer or any case of endometrial c ancer.
Inadvertent exposure to ionising radiation at absorbed doses > 100 mGy.
When the mother does not accept the marginally increased risks for malformations, mental retardation, stillbirth, IUGR associated with chemotherapy during pregnancy.
Cancer, fertility and pregnancy: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
Annals of Oncology 2011 G. Pentheroudakis, N. Pavlidis & M. Castiglione ESMO Guidelines Working Group