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NOVAK 34. Gestational Trophoblastic Disease

NOVAK 34. Gestational Trophoblastic Disease. 부산백병원 산부인과 R1 손영실. INDEX. # Persistent Gestational Trophoblastic Tumor 1. Nonmetastatic Disease 2. Metastatic Disease 3. Staging 4. Prognostic Scoring System 5. Diagnostic Evaluation

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NOVAK 34. Gestational Trophoblastic Disease

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  1. NOVAK 34. Gestational Trophoblastic Disease 부산백병원 산부인과 R1 손영실

  2. INDEX # Persistent Gestational Trophoblastic Tumor 1. Nonmetastatic Disease 2. Metastatic Disease 3. Staging 4. Prognostic Scoring System 5. Diagnostic Evaluation 6. Management of Persistent GTT # Chemotherapy 1. Single-agent Treatment 2. Combination Chemotherapy

  3. # Persistent Gestational Trophoblastic Tumor

  4. NONMETASTATIC DISEASE ◎ Locally invasive GTT : about 15% of patients after molar evacuation and after other gestations ◎ Symptoms ① irregular vaginal bleeding ② theca lutein cysts ③ uterine subinvolution or asymmetric enlargement ④ persistently elevated serum hCG levels ◎ Histology of persistent GTT ① after molar evacuation ⇒ H-mole or choriocarcinoma ② after nonmolar pregnancy ⇒ always choriocarcinoma

  5. METASTATIC DISEASE • 4% of patients after evacuation of a complete mole • usually associated with choriocarcinoma • early vascular invasion with widespread dissemination • spontaneous bleeding at meatstatic foci • metastatic site : lung(80%), vagina(30%), pelvis(20%), liver(10%), and brain(10%)

  6. METASTATIC DISEASE 1. Pulmonary • lung involvement is visible on chest x-ray of 80% of patients with metastatic GTT ① “snowstorm” pattern ② discrete rounded density ③ pleural effusion ④ an embolic pattern by pulmonary arterial occlusion • Sx : chest pain, cough, hemoptysis, dyspnea, or asymptomatic lesion 2. Vaginal • occurs in 30% of patients with metastatic tumor • highly vascular, may bleed vigorously if sample is taken for biopsy • Sx : irregular bleeding, purulent discharge

  7. METASTATIC DISEASE 3. Hepatic • 10% of patients • Sx : epigastric or RUQ pain (if metastases stretch the hepatic capsule) • hemorrhagic → causing hepatic rupture & intraperitoneal bleeding 4. CNS • 10% of patients • generally seen in patients with advanced disease • spontaneous bleeding → acute focal neurologic deficits

  8. STAGING - by FIGO classification ◎ Stage Ⅰ : patients have persistently elevated hCG levels and tumor confined to the uterine corpus ◎ Stage Ⅱ : patients have metastases to the vagina and pelvis or both ◎ Stage Ⅲ : patients have pulmonary metastases with or without uterine, vaginal, or pelvic involvement ◎ Stage Ⅳ : patients have advanced disease and involvement of the brain, liver, kidneys, or gastrointestinal tract

  9. STAGING

  10. PROGNOSTIC SCORING SYSTEM ◎ to consider other variables to predict the drug resistance to assist in selecting appropriate chemotherapy ◎ higher than 7 : categorized as high risk requires intensive combination chemotherapy

  11. PROGNOSTIC SCORING SYSTEM

  12. DIAGNOSTIC EVALUATION ◎ All patients with persistent GTT should undergo a careful pretreatment evaluation ① complete history and physical exam ② measurement of serum hCG level ③ hepatic, thyroid, and renal function test ④ determination of baseline peripheral WBC & platelet count ◎ The metastatic workup ① chest radiograph or CT scan ② ultrasonography or CT scan of the abdomen & pelvis ③ CT or MRI scan of the head ◎ When the pelvic exam & chest radiographic findings are negative, metastatic involvement of other sites is uncommon

  13. MANAGEMENT OF PERSISTENT GTT

  14. MANAGEMENT OF PERSISTENT GTT 1. Stage Ⅰ - the selection of Tx is based primarily on whether the patients desire to retain fertility A. Hysterectomy plus Chemotherapy • If patient does not wish to preserve fertility ⇒ hysterectomy + adjuvant single chemotherapy • Reasons of adjuvant chemotherapy ① to reduce disseminating viable tumor cells at surgery ② to maintain a cytotoxic level of chemotherapy in case viable tumor cells are disseminated at surgery ③ to treat any occult metastases that may already be present at surgery

  15. MANAGEMENT OF PERSISTENT GTT B. Chemotherapy Alone • In patients with stage Ⅰ who desire to retain fertility ⇒ single-agent chemotherapy ⇒ 92.1% of patients attained complete remission • Patients are resistant to single-agent chemotherapy (desire to retain fertility) ⇒ combination chemotherapy • If resistant to both ⇒ local uterine resection may be considered

  16. MANAGEMENT OF PERSISTENT GTT 2. Stage Ⅱ and Ⅲ - low-risk : single agent chemoTx - high-risk : combination chemoTx A. Vaginal and Pelvic Metastasis • vaginal metastases may bleed profusely (∵ highly vascular and friable) ⇒ controlled by packing or by wide local excision B. Pulmonary Metastasis • persistent viable pulmonary metastasis despite intensive chemotherapy ⇒ thoracotomy may be attempted to excise the resistant focus

  17. MANAGEMENT OF PERSISTENT GTT C. Hysterectomy • may be required in patients with metastases to control uterine hemorrhage or sepsis D. Follow-up (Stage Ⅰ ~ Ⅲ) ① weekly measurement of hCG levels until normal for 3 consecutive weeks ② monthly measurement of hCG values until normal for 12 consecutive months ③ effective contraception during the entire interval of hormonal follow-up

  18. MANAGEMENT OF PERSISTENT GTT 3. Stage Ⅳ - primary intensive combination chemotherapy and the selective use of radiation therapy and surgery A. Hepatic Metastasis • resistant to systemic chemotherapy → hepatic arterial infusion of chemotherapy • acute bleeding of tumor → hepatic resection

  19. MANAGEMENT OF PERSISTENT GTT B. Cerebral Metastasis • If diagnosed, whole-brain irradiation (3,000 cGy in 10 fractions) can be instituted promptly • conurrent use of combination chemotherapy and brain irradiation → spontaneous cerebral hemorrhage ↓ C. Follow-up (Stage Ⅳ) ① weekly determination of hCG levels until they are normal 3 consecutive weeks ② monthly determination of hCG levels until they are normal for 24 consecutive months • increased risk of late recurrence → prolonged gonadotropin follow-up is required

  20. GTN Mole Choriocarcinoma Evacuation and weekly hCG titers ↓ hCG titers ↑ or plateaud hCG titers Careful follow-up and contraception Metastatic work-up Uterine disease Pelvic metastasis Lung metastasis Distant metastasis Stage Ⅰ Stage Ⅱ Stage Ⅲ Stage Ⅳ Single drug chemotherapy or hysterectomy Calculate risk Combination chemotherapy ± surgery ± RT Low High Follow-up Resistant MANAGEMENT OF PERSISTENT GTT

  21. # Chemotherapy

  22. SINGLE-AGENT TREATMENT ◎ Nonmetastatic and low-risk GTT ⇒ actinomycin D (Act-D) or MTX has achieved comparable and excellent remission rates ◎ Protocols ① Act-D can be given every other week as a 5-day regimen or in a pulsatile fashion ② use of MTX was the same ◎ Methotrexate with folic acid (MTX-FA) ① the preferred single agent in the Tx of GTT ② remission rates - 90.2% in stage Ⅰ - 68.2% in low-risk stages Ⅱ & Ⅲ ③ after Tx with MTX-FA, thrombocytopenia, granulocytopenia and hepatotoxicity developed in only 1.6%, 5.9% and 14.1% of patients

  23. SINGLE-AGENT TREATMENT 1. Technique of Single-agent Treatment ◎ Serum hCG levels is measured weekly after each course of chemotherapy ◎ hCG regression curve serves as the primary basis for determining the need for additional Tx ◎ After 1st Tx ① Further chemotherapy is withheld as long as the hCG level is falling progressively ② Additional single-agent chemotherapy is not administered at any predetermined or fixed interval ◎ 2nd course of chemotherapy is administered under the following conditions ① If the hCG level plateaus for more than 3 conseutive weeks or begins to rise again ② If the hCG level does not decline by 1 log within 18 days after completion of the first treatment

  24. COMBINATION CHEMOTHERAPY 1. Triple Therapy ◎ etoposide, MTX, Act-D, cyclophosphamide and vincristine (EMA-CO) - had complete remission in patients with metastasis and a high-risk score (76~94%) - remission occurred in 13 of 15 patients (86%) with brain metastasis ◎ EMA-CO regimen ① the preferred primary Tx in patients with metastasis and a high-risk prognostic score ② generally well tolerated ③ seldom has to be suspended because of toxicity

  25. COMBINATION CHEMOTHERAPY 2. Duration of therapy ◎ Combination chemotherapy should be given as often as toxicity permits until the patients achieves three consecutive normal hCG levels ◎ After normal hCG levels are attained, at least two additional course are administered to reduce the risk of relapse

  26. 감사합니다.

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