Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Restricted access

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Individual Disclosures for the NCCN Gestational Trophoblastic Neoplasia Panel

TU1
  • 1.

    Altieri A, Franceschi S, Ferlay J, . Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 2003;4:670–678.

  • 2.

    Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol 2010;203:531–539.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet 2010;376:717–729.

  • 4.

    Brown J, Naumann RW, Seckl MJ, . 15years of progress in gestational trophoblastic disease: scoring, standardization, and salvage. Gynecol Oncol 2017;144:200–207.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Lurain JR. Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. Am J Obstet Gynecol 2011;204:11–18.

  • 6.

    Berkowitz RS, Goldstein DP. Current advances in the management of gestational trophoblastic disease. Gynecol Oncol 2013;128:3–5.

  • 7.

    Berkowitz RS, Goldstein DP. Chorionic tumors. N Engl J Med 1996;335:1740–1748.

  • 8.

    Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N Engl J Med 2009;360:1639–1645.

  • 9.

    Sun SY, Melamed A, Goldstein DP, . Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia? Gynecol Oncol 2015;138:46–49.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Horowitz NS, Goldstein DP, Berkowitz RS. Placental site trophoblastic tumors and epithelioid trophoblastic tumors: Biology, natural history, and treatment modalities. Gynecol Oncol 2017;144:208–214.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Shaaban AM, Rezvani M, Haroun RR, . Gestational trophoblastic disease: clinical and imaging features. Radiographics 2017;37:681–700.

  • 12.

    Hancock BW, Tidy JA. Current management of molar pregnancy. J Reprod Med 2002;47:347–354.

  • 13.

    Ngan HY, Seckl MJ, Berkowitz RS, . Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet 2015;131(Suppl 2):S123–S126.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Zhao P, Lu Y, Huang W, . Total hysterectomy versus uterine evacuation for preventing post-molar gestational trophoblastic neoplasia in patients who are at least 40 years old: a systematic review and meta-analysis. BMC Cancer 2019;19:13.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Wang Q, Fu J, Hu L, . Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2017;9:CD007289.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Berkowitz RS, Goldstein DP. Gestational trophoblastic disease. Cancer 1995; 76(10 Suppl)2079–2085.

  • 17.

    Cole LA. Human chorionic gonadotropin and associated molecules. Expert Rev Mol Diagn 2009;9:51–73.

  • 18.

    Ngan HYS, Seckl MJ, Berkowitz RS, . Update on the diagnosis and management of gestational trophoblastic disease. Int J Gynaecol Obstet 2018;143(Suppl 2):79–85.

  • 19.

    Muller CY, Cole LA. The quagmire of hCG and hCG testing in gynecologic oncology. Gynecol Oncol 2009;112:663–672.

  • 20.

    Coyle C, Short D, Jackson L, . What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients. Gynecol Oncol 2018;148:254–257.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Schmitt C, Doret M, Massardier J, . Risk of gestational trophoblastic neoplasia after hCG normalisation according to hydatidiform mole type. Gynecol Oncol 2013;130:86–89.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Braga A, Maestá I, Matos M, . Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation. Gynecol Oncol 2015;139:283–287.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    FIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. Int J Gynaecol Obstet 2002;77:285–287.

  • 24.

    Eysbouts YK, Massuger L, IntHout J, . The added value of hysterectomy in the management of gestational trophoblastic neoplasia. Gynecol Oncol 2017;145:536–542.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Doll KM, Soper JT. The role of surgery in the management of gestational trophoblastic neoplasia. Obstet Gynecol Surv 2013;68:533–542.

  • 26.

    Pezeshki M, Hancock BW, Silcocks P, . The role of repeat uterine evacuation in the management of persistent gestational trophoblastic disease. Gynecol Oncol 2004;95:423–429.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Garner EI, Feltmate CM, Goldstein DP, . The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol 2005;99:3–5.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    van Trommel NE, Thomas CM, Massuger LF, . Second curettage in persistent trophoblastic disease (PTD): the need for univocal definition of PTD. Gynecol Oncol 2005;99:250–251, author reply 251.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Osborne RJ, Filiaci VL, Schink JC, . Second curettage for low-risk nonmetastatic gestational trophoblastic neoplasia. Obstet Gynecol 2016;128:535–542.

  • 30.

    Savage P, Seckl MJ. The role of repeat uterine evacuation in trophoblast disease. Gynecol Oncol 2005;99:251–252, author reply 252–253.

  • 31.

    May T, Goldstein DP, Berkowitz RS. Current chemotherapeutic management of patients with gestational trophoblastic neoplasia. Chemother Res Pract 2011;2011:806256.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. Lancet 2000;355:712–715.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Cole LA, Muller CY. Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases. Gynecol Oncol 2010;116:3–9.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Ngan HY, Bender H, Benedet JL, .FIGO Committee on Gynecologic Oncology. Gestational trophoblastic neoplasia, FIGO 2000 staging and classification. Int J Gynaecol Obstet 2003;83(Suppl 1):175–177.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Gestational trophoblastic diseases. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser 1983;692:7–81.

  • 36.

    Bagshawe KD. Risk and prognostic factors in trophoblastic neoplasia. Cancer 1976;38:1373–1385.

  • 37.

    Goldstein DP, Berkowitz RS, Horowitz NS. Optimal management of low-risk gestational trophoblastic neoplasia. Expert Rev Anticancer Ther 2015;15:1293–1304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Mangili G, Lorusso D, Brown J, . Trophoblastic disease review for diagnosis and management: a joint report from the International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup. Int J Gynecol Cancer 2014; 24(9, Suppl 3)S109–S116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Lawrie TA, Alazzam M, Tidy J, . First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2016;6:CD007102.

  • 40.

    Schink JC, Filiaci V, Huang H, . A phase III randomized trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia [abstract]. Presented at the XIX World Congress of the International Society for the Study of Trophoblastic Diseases; September 21-24, 2017; Amsterdam, The Netherlands.

  • 41.

    Osborne RJ, Filiaci V, Schink JC, . Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol 2011;29:825–831.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Kohorn EI. Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy resistance? Gynecol Oncol 2002;85:36–39.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Sita-Lumsden A, Short D, Lindsay I, . Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009. Br J Cancer 2012;107:1810–1814.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Hitchins RN, Holden L, Newlands ES, . Single agent etoposide in gestational trophoblastic tumours: experience at Charing Cross Hospital 1978-1987. Eur J Cancer Clin Oncol 1988;24:1041–1046.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Sung HC, Wu PC, Yang HY. Reevaluation of 5-fluorouracil as a single therapeutic agent for gestational trophoblastic neoplasms. Am J Obstet Gynecol 1984;150:69–75.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Alazzam M, Tidy J, Osborne R, . Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2016;1:CD008891.

    • Search Google Scholar
    • Export Citation
  • 47.

    Covens A, Filiaci VL, Burger RA, . Phase II trial of pulse dactinomycin as salvage therapy for failed low-risk gestational trophoblastic neoplasia: a Gynecologic Oncology Group study. Cancer 2006;107:1280–1286.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    McNeish IA, Strickland S, Holden L, . Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol 2002;20:1838–1844.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    McGrath S, Short D, Harvey R, . The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l(-1). Br J Cancer 2010;102:810–814.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50.

    Lurain JR, Chapman-Davis E, Hoekstra AV, . Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia. J Reprod Med 2012;57:283–287.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Prouvot C, Golfier F, Massardier J, . Efficacy and safety of second-line 5-day dactinomycin in case of methotrexate failure for gestational trophoblastic neoplasia. Int J Gynecol Cancer 2018;28:1038–1044.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Alifrangis C, Agarwal R, Short D, . EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol 2013;31:280–286.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Lurain JR, Singh DK, Schink JC. Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy. J Reprod Med 2006;51:767–772.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Ahamed E, Short D, North B, . Survival of women with gestational trophoblastic neoplasia and liver metastases: is it improving? J Reprod Med 2012;57:262–269.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Newlands ES, Holden L, Seckl MJ, . Management of brain metastases in patients with high-risk gestational trophoblastic tumors. J Reprod Med 2002;47:465–471.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Crawford RA, Newlands E, Rustin GJ, . Gestational trophoblastic disease with liver metastases: the Charing Cross experience. Br J Obstet Gynaecol 1997;104:105–109.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 57.

    Newlands ES, Bagshawe KD, Begent RH, . Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989. Br J Obstet Gynaecol 1991;98:550–557.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Bolis G, Bonazzi C, Landoni F, . EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT). Gynecol Oncol 1988;31:439–444.

  • 59.

    Kim SJ, Bae SN, Kim JH, . Risk factors for the prediction of treatment failure in gestational trophoblastic tumors treated with EMA/CO regimen. Gynecol Oncol 1998;71:247–253.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Matsui H, Suzuka K, Iitsuka Y, . Combination chemotherapy with methotrexate, etoposide, and actinomycin D for high-risk gestational trophoblastic tumors. Gynecol Oncol 2000;78:28–31.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61.

    Escobar PF, Lurain JR, Singh DK, . Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy. Gynecol Oncol 2003;91:552–557.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    Turan T, Karacay O, Tulunay G, . Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Cancer 2006;16:1432–1438.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Lu WG, Ye F, Shen YM, . EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients. Int J Gynecol Cancer 2008;18:357–362.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Cagayan MS. High-risk metastatic gestational trophoblastic neoplasia: primary management with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy. J Reprod Med 2012;57:231–236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65.

    Cyriac S, Rajendranath R, Sridevi V, . Etoposide, cisplatin-etoposide, methotrexate, actinomycin-D as primary treatment for management of very-high-risk gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2011;115:37–39.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66.

    Ghaemmaghami F, Modares M, Arab M, . EMA-EP regimen, as first line multiple agent chemotherapy in high-risk GTT patients (stage II-IV). Int J Gynecol Cancer 2004;14:360–365.

    • Search Google Scholar
    • Export Citation
  • 67.

    Han SN, Amant F, Leunen K, . EP-EMA regimen (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia. Int J Gynecol Cancer 2012;22:875–880.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 68.

    Dobson LS, Lorigan PC, Coleman RE, . Persistent gestational trophoblastic disease: results of MEA (methotrexate, etoposide and dactinomycin) as first-line chemotherapy in high risk disease and EA (etoposide and dactinomycin) as second-line therapy for low risk disease. Br J Cancer 2000;82:1547–1552.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 69.

    Curry SL, Blessing JA, DiSaia PJ, . A prospective randomized comparison of methotrexate, dactinomycin, and chlorambucil versus methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine in “poor prognosis” metastatic gestational trophoblastic disease: a Gynecologic Oncology Group study. Obstet Gynecol 1989;73:357–362.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Zhao Y, Zhang W, Duan W. Management of gestational trophoblastic neoplasia with 5-fluorouracil and actinomycin D in northern China. J Reprod Med 2009;54:88–94.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71.

    Wang S, An R, Han X, . Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: a report based on our 11-year clinical experiences. Gynecol Oncol 2006;103:1105–1108.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72.

    Deng L, Yan X, Zhang J, . Combination chemotherapy for high-risk gestational trophoblastic tumour. Cochrane Database Syst Rev 2009; (2):CD005196.

  • 73.

    Kong Y, Yang J, Jiang F, . Clinical characteristics and prognosis of ultra high-risk gestational trophoblastic neoplasia patients: a retrospective cohort study. Gynecol Oncol 2017;146:81–86.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Bolze PA, Riedl C, Massardier J, . Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13. Am J Obstet Gynecol 2016;214: 390.e391–390.e8.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 75.

    Savage P, Kelpanides I, Tuthill M, . Brain metastases in gestational trophoblast neoplasia: an update on incidence, management and outcome. Gynecol Oncol 2015;137:73–76.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 76.

    Gavanier D, Leport H, Massardier J, . Gestational trophoblastic neoplasia with brain metastasis at initial presentation: a retrospective study. Int J Clin Oncol 2019;24:153–160.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77.

    Piura E, Piura B. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature. Eur J Gynaecol Oncol 2014;35:359–367.

  • 78.

    Neubauer NL, Latif N, Kalakota K, . Brain metastasis in gestational trophoblastic neoplasia: an update. J Reprod Med 2012;57:288–292.

  • 79.

    Soper JT, Spillman M, Sampson JH, . High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients. Gynecol Oncol 2007;104:691–694.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 80.

    Rustin GJ, Newlands ES, Begent RH, . Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma. J Clin Oncol 1989;7:900–903.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 81.

    Evans AC, Jr., Soper JT, Clarke-Pearson DL, . Gestational trophoblastic disease metastatic to the central nervous system. Gynecol Oncol 1995;59:226–230.

  • 82.

    Small W, Jr., Lurain JR, Shetty RM, . Gestational trophoblastic disease metastatic to the brain. Radiology 1996;200:277–280.

  • 83.

    Bakri Y, Berkowitz RS, Goldstein DP, . Brain metastases of gestational trophoblastic tumor. J Reprod Med 1994;39:179–184.

  • 84.

    Alazzam M, Hancock BW, Tidy J. Role of hysterectomy in managing persistent gestational trophoblastic disease. J Reprod Med 2008;53:519–524.

  • 85.

    Fleming EL, Garrett L, Growdon WB, . The changing role of thoracotomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center. J Reprod Med 2008;53:493–498.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 86.

    Kanis MJ, Lurain JR. Pulmonary resection in the management of high-risk gestational trophoblastic neoplasia. Int J Gynecol Cancer 2016;26:796–800.

  • 87.

    Mapelli P, Mangili G, Picchio M, . Role of 18F-FDG PET in the management of gestational trophoblastic neoplasia. Eur J Nucl Med Mol Imaging 2013;40:505–513.

  • 88.

    Lim AK, Agarwal R, Seckl MJ, . Embolization of bleeding residual uterine vascular malformations in patients with treated gestational trophoblastic tumors. Radiology 2002;222:640–644.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 89.

    Tse KY, Chan KK, Tam KF, . 20-year experience of managing profuse bleeding in gestational trophoblastic disease. J Reprod Med 2007;52:397–401.

  • 90.

    McGrath S, Harding V, Lim AK, . Embolization of uterine arteriovenous malformations in patients with gestational trophoblastic tumors: a review of patients at Charing Cross Hospital, 2000-2009. J Reprod Med 2012;57:319–324.

    • Search Google Scholar
    • Export Citation
  • 91.

    Lurain JR, Singh DK, Schink JC. Role of surgery in the management of high-risk gestational trophoblastic neoplasia. J Reprod Med 2006;51:773–776.

  • 92.

    Powles T, Savage PM, Stebbing J, . A comparison of patients with relapsed and chemo-refractory gestational trophoblastic neoplasia. Br J Cancer 2007;96:732–737.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 93.

    Hoekstra AV, Lurain JR, Rademaker AW, . Gestational trophoblastic neoplasia: treatment outcomes. Obstet Gynecol 2008;112:251–258.

  • 94.

    Lurain JR, Casanova LA, Miller DS, . Prognostic factors in gestational trophoblastic tumors: a proposed new scoring system based on multivariate analysis. Am J Obstet Gynecol 1991;164:611–616.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 95.

    Lurain JR, Hoekstra AV, Schink JC. Results of treatment of patients with gestational trophoblastic neoplasia referred to the Brewer Trophoblastic Disease Center after failure of treatment elsewhere (1979-2006). J Reprod Med 2008;53:535–540.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 96.

    Lurain JR, Schink JC. Importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia. J Reprod Med 2012;57:219–224.

  • 97.

    Newlands ES, Mulholland PJ, Holden L, . Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors. J Clin Oncol 2000;18:854–859.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 98.

    Mao Y, Wan X, Lv W, . Relapsed or refractory gestational trophoblastic neoplasia treated with the etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EP-EMA) regimen. Int J Gynaecol Obstet 2007;98:44–47.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 99.

    Anantharaju AA, Pallavi VR, Bafna UD, . Role of salvage therapy in chemo resistant or recurrent high-risk gestational trophoblastic neoplasm. Int J Gynecol Cancer 2019;29:547–553.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 100.

    Lurain JR, Singh DK, Schink JC. Management of metastatic high-risk gestational trophoblastic neoplasia: FIGO stages II-IV: risk factor score > or = 7. J Reprod Med 2010;55:199–207.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 101.

    Wang J, Short D, Sebire NJ, . Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol 2008;19:1578–1583.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 102.

    Essel KG, Bruegl A, Gershenson DM, . Salvage chemotherapy for gestational trophoblastic neoplasia: utility or futility? Gynecol Oncol 2017;146:74–80.

  • 103.

    Feldman DR, Hu J, Dorff TB, . Paclitaxel, ifosfamide, and cisplatin efficacy for first-line treatment of patients with intermediate- or poor-risk germ cell tumors. J Clin Oncol 2016;34:2478–2483.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 104.

    Mardiak J, Rejlekova K, Mego M, . Determination of efficacy of TIP combination (paclitaxel, ifosfamide, cisplatin) as first salvage therapy for patients with relapsed germ cell tumors in a poor prognosis group [published online December 12, 2016]. J Clin Oncol doi: 10.1200/jco.2009.27.15_suppl.e16049

    • Crossref
    • Export Citation
  • 105.

    Kondagunta GV, Bacik J, Donadio A, . Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol 2005;23:6549–6555.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 106.

    Motzer RJ, Sheinfeld J, Mazumdar M, . Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 2000;18:2413–2418.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 107.

    Lurain JR, Nejad B. Secondary chemotherapy for high-risk gestational trophoblastic neoplasia. Gynecol Oncol 2005;97:618–623.

  • 108.

    Benigno BB. High-dose chemotherapy with autologous stem cell support as salvage therapy in recurrent gestational trophoblastic disease. Int J Gynecol Cancer 2013;23:1331–1333.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 109.

    El-Helw LM, Seckl MJ, Haynes R, . High-dose chemotherapy and peripheral blood stem cell support in refractory gestational trophoblastic neoplasia. Br J Cancer 2005;93:620–621.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 110.

    Frijstein MM, Lok CAR, Short D, . The results of treatment with high-dose chemotherapy and peripheral blood stem cell support for gestational trophoblastic neoplasia. Eur J Cancer 2019;109:162–171.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 111.

    van Besien K, Verschraegen C, Mehra R, . Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue. Gynecol Oncol 1997;65:366–369.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 112.

    Yamamoto E, Niimi K, Fujikake K, . High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: a case report and literature review. Mol Clin Oncol 2016;5:660–664.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 113.

    Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016;39:98–106.

  • 114.

    Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res 2012;18:6580–6587.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 115.

    Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492–499.

  • 116.

    Bolze PA, Patrier S, Massardier J, . PD-L1 expression in premalignant and malignant trophoblasts from gestational trophoblastic diseases is ubiquitous and independent of clinical outcomes. Int J Gynecol Cancer 2017;27:554–561.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 117.

    Veras E, Kurman RJ, Wang TL, . PD-L1 expression in human placentas and gestational trophoblastic diseases. Int J Gynecol Pathol 2017;36:146–153.

  • 118.

    Ghorani E, Kaur B, Fisher RA, . Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet 2017;390:2343–2345.

  • 119.

    Pandian Z, Seckl MJ, Smith R, . Gestational choriocarcinoma: an unusual presentation with response to gemcitabine and surgery. BJOG 2004;111:382–384.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 120.

    Bianconi MI, Otero S, Storino C, . Role of capecitabine in the management of gestational trophoblastic neoplasia: a drug for two settings. J Reprod Med 2017;62:250–256.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 121.

    Bianconi M, Jankilevich G, Otero S, . Successful salvage of a relapsed high risk gestational trophoblastic neoplasia patient using capecitabine. Gynecol Oncol 2007;106:268–271.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 122.

    Zhang Y, Zhang S, Huang W, . Intermediate trophoblastic tumor: the clinical analysis of 62 cases and prognostic factors. Arch Gynecol Obstet 2019;299:1353–1364.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 123.

    Lan C, Li Y, He J, . Placental site trophoblastic tumor: lymphatic spread and possible target markers. Gynecol Oncol 2010;116:430–437.

  • 124.

    Frijstein MM, Lok CAR, van Trommel NE, .all the contributors to the ISSTD PSTT/ETT database. Management and prognostic factors of epithelioid trophoblastic tumors: results from the International Society for the Study of Trophoblastic Diseases database. Gynecol Oncol 2019;152:361–367.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 125.

    Kurman RJ, Shih IeM. Discovery of a cell: reflections on the checkered history of intermediate trophoblast and update on its nature and pathologic manifestations. Int J Gynecol Pathol 2014;33:339–347.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 126.

    Schmid P, Nagai Y, Agarwal R, . Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 2009;374:48–55.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 127.

    Zhao J, Lv WG, Feng FZ, . Placental site trophoblastic tumor: a review of 108 cases and their implications for prognosis and treatment. Gynecol Oncol 2016;142:102–108.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 128.

    Froeling FEM, Ramaswami R, Papanastasopoulos P, . Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours. Br J Cancer 2019;120:587–594.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 129.

    Baergen RN, Rutgers JL, Young RH, . Placental site trophoblastic tumor: a study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006;100:511–520.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 130.

    Papadopoulos AJ, Foskett M, Seckl MJ, . Twenty-five years’ clinical experience with placental site trophoblastic tumors. J Reprod Med 2002;47:460–464.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 131.

    Hassadia A, Gillespie A, Tidy J, . Placental site trophoblastic tumour: clinical features and management. Gynecol Oncol 2005;99:603–607.

  • 132.

    Shih IM, Kurman RJ. Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 1998;22:1393–1403.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 133.

    Allison KH, Love JE, Garcia RL. Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast. Arch Pathol Lab Med 2006;130:1875–1877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 134.

    Yang J, Zong L, Wang J, . Epithelioid trophoblastic tumors: treatments, outcomes, and potential therapeutic targets. J Cancer 2019;10:11–19.

  • 135.

    Hancock B, Froeling FEM, Ramaswami R, . The ISSTD global placental site and epithelioid trophoblastic tumor (PSTT/ETT) database – an analysis of 326 patients. Presented at the ISSTD XVIII World Congress on Gestational Trophoblastic Disease; 2015; Bali, Indonesia.

  • 136.

    Sobecki-Rausch J, Winder A, Maniar KP, . Surgery and platinum/etoposide-based chemotherapy for the treatment of epithelioid trophoblastic tumor. Int J Gynecol Cancer 2018;28:1117–1122.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 2521 2522 1882
PDF Downloads 752 752 609
EPUB Downloads 0 0 0