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    EASO2011 PanArab 4 Pentheroudakis EASO2011 PanArab 4 Pentheroudakis Presentation Transcript

    • Melanoma and Gastrointestinal cancer during pregnancy George Pentheroudakis Assistant Professor of Oncology Medical School, University of Ioannina Greece
    • Physician Reaction
      • 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
    • Surgery
      • Cohen-Kerem et al,
      • Ann Surg Oncol 2005
      • n=12,542
      • Mazzle et al,
      • Am J Obstet Gynecol
      • n=5,405
      • 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.
    •  
    • M anagement
      • 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.
    • SLNB?
      • 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.
    • Most common GI malignancies in pregnancy
      • Colorectal cancer: 1:13000 pregnancies, 350 cases reported.
      • Gastric cancer: Very rare, 150 cases reported.
      • Pancreatic cancer: Exceedingly rare.
      • Hepatoma: Exceedingly rare, 45 cases reported.
    • Peculiarities
      • Colorectal cancer: 50-80% incidence of rectal cancers. 50-70% high-grade, mucinous tumours. Frequent ovarian deposits.
      • Gastric cancer: High-grade, Lauren Diffuse type, retroperitoneal/peritoneal deposits common, liver mets rare
      • Pancreatic cancer: Advanced stage at presentation
      • Hepatoma: HCV-related in West, HBV-related in Africa and Asia. Fitter pts, short lag-time from viral infection to tumour, low serum AFP.
    • Symptoms and presentation
      • Colorectal cancer: Diarrhoea, constipation, bleeding, nausea, pain, weight-loss.
      • Gastric cancer: nausea, vomiting, anorexia, weight loss, epigastric pain.
      • Pancreatic cancer: jaundice, nausea, vomiting, weight loss, epigastric discomfort.
      • Hepatoma: Fatigue, ascites, nausea/vomiting, right upper quadrant pain and hypoglycemia
    • Gastric cancer
    • Diagnostic work-up
      • 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
      • Surgery
        • 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
      • OR
      • pregnancy termination and surgery
      • OR
      • attempt at surgery and continuation of pregnancy.
      • RT only possible after pregnancy termination or post partum
    • Advanced disease
      • 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.
    • Prognosis
      • 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.
    • Clinical recommendations
      • 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