EASO2011 PanArab 4 Pentheroudakis


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EASO2011 PanArab 4 Pentheroudakis

  1. 1. Melanoma and Gastrointestinal cancer during pregnancy George Pentheroudakis Assistant Professor of Oncology Medical School, University of Ioannina Greece
  2. 2. Physician Reaction <ul><li>Ob/Gyn: Oh No! She has cancer! </li></ul><ul><li>Med Onc: Oh No! She’s pregnant! </li></ul><ul><li>Surgeon/Primary Care: Oh No! She’s pregnant and has cancer! </li></ul>
  5. 5. RECOMMENDED STAGING IMAGING TESTS IN PREGNANT WOMEN WITH CANCER <ul><li> Abdominal plain films, isotope scans, PET scans and CT-scans should be avoided . </li></ul><ul><li> Chest X-ray and abdominal ultrasound can be indicated and are safe. </li></ul><ul><li>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. </li></ul>
  6. 6. 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
  7. 7. Surgery <ul><li>Cohen-Kerem et al, </li></ul><ul><li>Ann Surg Oncol 2005 </li></ul><ul><li>n=12,542 </li></ul><ul><li>Mazzle et al, </li></ul><ul><li>Am J Obstet Gynecol </li></ul><ul><li>n=5,405 </li></ul><ul><li>Surgery is effective and safe in pregnant women. </li></ul><ul><li>Highest risk of abortion (10%) with first-trimester or abdominopelvic operations. </li></ul>
  8. 8. Melanoma and pregnancy <ul><li>1/3 of malignant melamonas in women occur during child-bearing years. </li></ul><ul><li>Swedish Cancer Registry 1973-1984: Melanoma was the most common tumour of pregnant women (25% of total). </li></ul><ul><li>Presentation: Mostly ABCD </li></ul><ul><li>Lens et al, 2004: Thicker tumours diagnosed. </li></ul><ul><li>Mostly superficial spreading and nodular melanomas. </li></ul><ul><li>Diagnosis: Excisional biopsy safe. </li></ul>
  9. 10. M anagement <ul><li>Wide local excision with 1-2 cm margins under general or regional anesthesia. </li></ul><ul><li>Stage I-II: ELND or SLNB probably safe. Survival benefit has not been proven (MSLT-1 trial). </li></ul><ul><li>Stage III-IV: Therapeutic lymph node dissection should be performed, as well as resection of satellite, in-transit or isolated metastases. </li></ul>
  10. 11. SLNB? <ul><li>Isosulfan blue or methylene blue not recommended during pregnancy. </li></ul><ul><li>Gentillini et al, Ann Oncol 2004;15:1348- </li></ul><ul><li>Keleher et al, Breast J 2004;10:492: </li></ul><ul><li>Tc99m-Sulfur colloid: Fetal dose probably <4 mGy. </li></ul><ul><li>Lyman et al, JCO 2005;23;7703: </li></ul><ul><li>Probably safe, not enough evidence for sensitivity and safety in pregnant women though. </li></ul><ul><li>Should be considered experimental. </li></ul>
  11. 12. Effect of pregnancy on melanoma <ul><li>Pack et al, 1951: Mortality 50%! </li></ul><ul><li>5 controlled studies failed to show inferior survival of pregnant women with melanoma compared to matched non-pregnant patients. </li></ul><ul><li>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 </li></ul>
  12. 13. Survival of pregnant vs non-pregnant age- stage-matched patients with melanoma; California Cancer Registry 1991-1999
  13. 15. 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.
  14. 16. Most common GI malignancies in pregnancy <ul><li>Colorectal cancer: 1:13000 pregnancies, 350 cases reported. </li></ul><ul><li>Gastric cancer: Very rare, 150 cases reported. </li></ul><ul><li>Pancreatic cancer: Exceedingly rare. </li></ul><ul><li>Hepatoma: Exceedingly rare, 45 cases reported. </li></ul>
  15. 17. Peculiarities <ul><li>Colorectal cancer: 50-80% incidence of rectal cancers. 50-70% high-grade, mucinous tumours. Frequent ovarian deposits. </li></ul><ul><li>Gastric cancer: High-grade, Lauren Diffuse type, retroperitoneal/peritoneal deposits common, liver mets rare </li></ul><ul><li>Pancreatic cancer: Advanced stage at presentation </li></ul><ul><li>Hepatoma: HCV-related in West, HBV-related in Africa and Asia. Fitter pts, short lag-time from viral infection to tumour, low serum AFP. </li></ul>
  16. 18. Symptoms and presentation <ul><li>Colorectal cancer: Diarrhoea, constipation, bleeding, nausea, pain, weight-loss. </li></ul><ul><li>Gastric cancer: nausea, vomiting, anorexia, weight loss, epigastric pain. </li></ul><ul><li>Pancreatic cancer: jaundice, nausea, vomiting, weight loss, epigastric discomfort. </li></ul><ul><li>Hepatoma: Fatigue, ascites, nausea/vomiting, right upper quadrant pain and hypoglycemia </li></ul>
  17. 19. Gastric cancer
  18. 20. Diagnostic work-up <ul><li>Colorectal cancer: Abdo/pelvic US, CXR, colonoscopy and biopsy, TRUS. </li></ul><ul><li>MRI without gadolinium in 1 st trimester. </li></ul><ul><li>Gastric cancer: US, transesophageal US, CXR, endoscopy with biopsy. </li></ul><ul><li>Pancreatic cancer: MRCP, US, CXR. ERCP with fluoroscopy not allowed in 1 st trimester. </li></ul><ul><li>Hepatoma: US, MRI. </li></ul>
  19. 21. Colorectal cancer during pregnancy
  20. 22. Management of localised disease during first 20-24 weeks <ul><li>Surgery </li></ul><ul><ul><li>If possible, wait beyond first 8-12 weeks for abdominal surgery. SAB: 20%  3% </li></ul></ul><ul><ul><li>Don’t remove corpus luteum if possible until the 14th week (progesterone supp. 50mg BID) </li></ul></ul><ul><ul><li>Deliver at maturity (at around 34-36 weeks) </li></ul></ul><ul><ul><li>No proven teratogenic effects of anesthesia </li></ul></ul>
  21. 23. Management of localised disease after first 24 weeks of gestation <ul><li>Watch-and-wait till delivery in week 32-34 and surgery </li></ul><ul><li>OR </li></ul><ul><li>pregnancy termination and surgery </li></ul><ul><li>OR </li></ul><ul><li>attempt at surgery and continuation of pregnancy. </li></ul><ul><li>RT only possible after pregnancy termination or post partum </li></ul>
  22. 24. Advanced disease <ul><li>Termination of pregnancy and chemotherapy during 1 st trimester </li></ul><ul><li>Chemotherapy in 2 nd and 3 rd trimesters safe </li></ul><ul><li>Only case reports on bevacizumab, cetuximab, erlotinib, oxaliplatin </li></ul><ul><li>Pre-eclampsia is caused by high levels of VEGF inhibitors! </li></ul>
  23. 25. Emergency procedures and Abortion <ul><li>An emergency laparotomy may be necessary upon occurrence of acute intestinal bleeding, perforation or obstruction </li></ul><ul><li>The indications for delivery by means of cesarean section are identical to those of the general population, with two additional ones: </li></ul><ul><li>- the presence of a bulky rectal cancer that compromises the birth canal </li></ul><ul><li>- the risk for extension of the perineotomy wound into a large anterior rectal carcinoma. </li></ul>
  24. 26. Prognosis <ul><li>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. </li></ul><ul><li>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. </li></ul>
  25. 27. 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
  26. 28. <ul><li>Sections of placenta show multiple aggregates of atypical epithelioid cells in the intervillous space. (Hematoxylin-eosin stain; original magnification X 100) </li></ul>A MELANOMA CASE
  27. 29. RECOMMENDATIONS FOR THERAPEUTIC ABORTION <ul><li>Whenever treatment should be given during 1 st trimester:. </li></ul><ul><li>Advanced malignancy and poor life expectancy . </li></ul><ul><li>Non-early stages of cervical , ovarian cancer or any case of endometrial c ancer. </li></ul><ul><li>Inadvertent exposure to ionising radiation at absorbed doses > 100 mGy. </li></ul><ul><li>When the mother does not accept the marginally increased risks for malformations, mental retardation, stillbirth, IUGR associated with chemotherapy during pregnancy. </li></ul>
  28. 30. Clinical recommendations <ul><li>Cancer, fertility and pregnancy: ESMO Clinical Recommendations for diagnosis, treatment and follow-up </li></ul>Annals of Oncology 2011 G. Pentheroudakis, N. Pavlidis & M. Castiglione ESMO Guidelines Working Group