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How to optimize the management of gestational trophoblastic disease during the coronavirus disease era?

  • Antonio Braga
    Affiliations
    Rio de Janeiro Trophoblastic Disease Center, Maternity School of Rio de Janeiro Federal University, Antonio Pedro University Hospital of Fluminense Federal University, Rua Laranjeiras, 180, Laranjeiras, Rio de Janeiro 22240-003, Brazil
    Postgraduate Program in Medical Sciences, Department of Maternal and Child Health, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
    Postgraduate Program in Perinatal Health, Faculty of Medicine, Rio de Janeiro Federal University, Brazil
    Task Force on COVID-19, Municipal Health Department, Rio de Janeiro, Brazil
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  • Kevin M. Elias
    Affiliations
    Special Pathogens Intensive Care Unit for COVID-19, Division of Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
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  • Kevin M. Elias
    Affiliations
    New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA
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  • Neil S. Horowitz
    Affiliations
    New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA
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  • Ross S. Berkowitz
    Affiliations
    New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, MA
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      To the Editors:
      Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the entire global health system was mobilized to care for these cases. This situation has had a major impact on the management of gestational trophoblastic diseases (GTD), both molar pregnancy (MP) and gestational trophoblastic neoplasia (GTN). In this letter, we highlight the main changes in GTD management in 2 of the largest reference centers in the Western Hemisphere, where COVID-19 is common (United States and Brazil).
      The greatest impact of COVID-19 is the imposition of quarantine where only essential medical services are fully operational. With limited nonemergency imaging services, we can expect a delayed diagnosis of MP leading to the appearance of medical complications historically seen at ≥12 weeks of gestation.
      • Sun S.Y.
      • Melamed A.
      • Goldstein D.P.
      • et al.
      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?.
      Even asymptomatic MP should be considered a medical emergency. After diagnosis, molar evacuation should be performed promptly, to avoid complications.
      Before the COVID-19 pandemic, postmolar follow-up consisted of weekly human chorionic gonadotropin (hCG) serum monitoring and periodic in person checkups. During the pandemic, we believe it is appropriate to use telemedicine for uncomplicated postmolar follow-up. To minimize risk of viral exposure during hCG collection, we suggest biweekly monitoring, as long as the hCG is progressively falling. In cases where the hCG begins to plateau or reelevate, weekly hormonal surveillance should resume. In addition, we have adopted early discharge from hCG monitoring for patients with MP. For those with a partial mole, discharge is possible after a single confirmatory normal hCG 1 month after remission (remission is defined as 3 prior weekly hCG measurements of <5 IU/L); and for those with a complete mole, discharge is possible after 3 normal monthly hCG values after remission are compared with the current standard of 6 months.
      • Horowitz N.S.
      • Berkowitz R.S.
      • Elias K.M.
      Considering changes in the recommended human chorionic gonadotropin monitoring after molar evacuation.
      Patients with GTN who are asymptomatic should not delay the start of chemotherapy owing to the theoretical risk of infection; if they have received positive test results for COVID-19 and are symptomatic, at the beginning or during the treatment, chemotherapy should be postponed, at least until respiratory symptoms have resolved.
      American Society of Clinical Oncology
      COVID-19 patient care information.
      ,
      • Pothuri B.
      • Alvarez Secord A.
      • Armstrong D.K.
      • et al.
      Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis.
      We recommend starting treatment with bolus dose of actinomycin D (Act-D) 1.25 mg/m2 biweekly during the pandemic for patients at low-risk of experiencing GTN. This regimen requires fewer medical visits and may lead to a higher response rate and shorter time to remission compared with those of methotrexate (MTX).
      • Pothuri B.
      • Alvarez Secord A.
      • Armstrong D.K.
      • et al.
      Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis.
      Multiagent chemotherapy (usually etoposide, MTX, Act-D, cyclophosphamide, and vincristine) is used as primary treatment for patients at high-risk of experiencing GTN. Patients undergoing multiagent regimen should be carefully monitored and treated for neutropenia and immunosuppression, because oncologic patients are more susceptible to COVID-19 and are at higher risk of experiencing severe disease, being admitted to the intensive care unit, and dying.
      • Yu J.
      • Ouyang W.
      • Chua M.L.K.
      • et al.
      SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China.
      To avoid immunosuppression, we recommend the routine use of granulocyte colony–stimulating factor during multiagent chemotherapy treatment.
      American Society of Clinical Oncology
      COVID-19 patient care information.
      During chemotherapy, the most serious manifestation of COVID-19 may be pneumonia, especially in the first 14 days after chemotherapy. In general, we recommend holding chemotherapy during treatment for COVID-19, except for patients with considerable pulmonary metastases, in whom treating these lesions might improve respiratory function.
      Although there are important challenges to treating patients with GTD during the pandemic, the proposed recommendations are intended to maximize the essential care for these patients.

      References

        • Sun S.Y.
        • Melamed A.
        • Goldstein D.P.
        • et al.
        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
        • Horowitz N.S.
        • Berkowitz R.S.
        • Elias K.M.
        Considering changes in the recommended human chorionic gonadotropin monitoring after molar evacuation.
        Obstet Gynecol. 2020; 135: 9-11
        • American Society of Clinical Oncology
        COVID-19 patient care information.
        (Available at:)
        • Pothuri B.
        • Alvarez Secord A.
        • Armstrong D.K.
        • et al.
        Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis.
        Gynecol Oncol. 2020; ([Epub ahead of print])
        • Yu J.
        • Ouyang W.
        • Chua M.L.K.
        • et al.
        SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China.
        JAMA Oncol. 2020; ([Epub ahead of print])