Metastatic Gestational Trophoblastic Neoplasia Leading to Acute Respiratory Failure and Death: A Case Report - About a Particularly Challenging Management in the Intensive Care Unit, and Exploring the Potential of Pembrolizumab in Treating Frail, Pretreated Gestational Trophoblastic Neoplasia. - 2025
Metastatic Gestational Trophoblastic Neoplasia Leading to Acute Respiratory Failure and Death: A Case Report - About a Particularly Challenging Management in the Intensive Care Unit, and Exploring the Potential of Pembrolizumab in Treating Frail, Pretreated Gestational Trophoblastic Neoplasia.
[en] [en] INTRODUCTION: Gestational trophoblastic disease (GTD) includes rare tumors from abnormal fertilization, ranging from benign hydatidiform moles to malignant choriocarcinomas (CCs) and rare placental-site trophoblastic tumors. Management of GTD depends on FIGO scoring, with low-risk cases treated conservatively and high-risk or ultra-high-risk cases requiring multi-agent chemotherapy, often EMA-CO, with induction therapy recommended for patients at very high risk of early death.
CASE PRESENTATION: We present the case of a 37-year-old female patient who developed an acute respiratory failure, requiring mechanical ventilation, 2 months after term delivery by cesarean section. The diagnosis of gestational trophoblastic neoplasia (GTN) was suspected due to high level of HCG in postpartum period and thoracic imaging suggesting multiple pulmonary metastases. No biopsy was available. She subsequently developed ventilator-associated pneumonia with severe acute respiratory distress syndrome (ARDS), requiring veno-venous extracorporeal membrane oxygenation support alongside concurrent polychemotherapy. After spending 61 days in the intensive care unit, and achieving biological complete remission based on HCG monitoring, the patient was transferred to the oncology ward. Due to prolonged hypoperfusion and hypoxemia, the patient developed ischemic cholangiopathy, severely constraining further therapeutic options. After 4 months of biological remission, the patient experienced a recurrence based on HCG rising and reappearing of pulmonary lesions on thoracic imaging in the lungs. In second line, the patient was treated with carboplatin, with no significant response. In third line, pembrolizumab was used, and the patient experienced a significant decrease in HCG. However, due to hematologic toxicity, we discontinued the treatment. Subsequently, the HCG level raised and the patient rapidly developed hemorrhagic cerebral metastasis and succumbed shortly thereafter.
CONCLUSION: This case underscores the importance of prompt recognition and timely intervention in the management of patients with ARDS during the early postpartum period. GTN with lung involvement should be considered after excluding the other more frequent causes of ARDS. It also highlights how ECMO support enables the continuation of chemotherapy and the achievement of remission in CC. Furthermore, due to the inability to initiate the desired chemotherapy, immunotherapy was introduced as a possible treatment modality. Therefore, this case underscores the importance of adaptability in treatment plans based on patient-specific clinical conditions and collaborative decision-making with specialized centers. Finally, it emphasizes the efficacy of pembrolizumab, even as a monotherapy, in pretreated CC cases.
Disciplines :
Oncology Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Meyers, Michel; Department of Medical Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Awada, Ahmad; Department of Medical Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Najmaoui, Marine; Department of Internal Medicine, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Ilzkovitz, Maxime; Department of Internal Medicine, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Pezzullo, Martina; Department of Radiology, Hôpital Erasme, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Chaves, Julia; Department of Gastroenterology, Hôpital Erasme, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Deviere, Jacques; Department of Gastroenterology, Hôpital Erasme, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Halenarova, Katarina; Department of Intensive Care, Hôpital Erasme, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Georgala, Aspasia; Department of Infectious Disease, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Fastrez, Maxime; Department of Gynecology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Goffin, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie-obstétrique, partim Gynécologie ; Belgium Registery and Reference Center for Gestational Trophoblastic Diseases, Liège, Belgium
Polastro, Laura; Department of Medical Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Language :
English
Title :
Metastatic Gestational Trophoblastic Neoplasia Leading to Acute Respiratory Failure and Death: A Case Report - About a Particularly Challenging Management in the Intensive Care Unit, and Exploring the Potential of Pembrolizumab in Treating Frail, Pretreated Gestational Trophoblastic Neoplasia.
Ngan HYS, Seckl MJ, Berkowitz RS, Xiang Y, Golfier F, Sekharan PK, et al. Diagnosis and management of gestational trophoblastic disease: 2021 update. Int J Gynaecol Obstet. 2021;155(Suppl 1):86–93. https://doi.org/10.1002/ijgo.13877
Schmid P, Nagai Y, Agarwal R, Hancock B, Savage PM, Sebire NJ, et al. Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Prognostic Markers Long-term Outcome Placental-site Trophoblastic Tumours: A Retrospective Observational Study Lancet. 2009; 374(9683):48–55. https://doi.org/10.1016/S0140-6736(09)60618-8
Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. déc. 2010;203(6):531–9. https://doi.org/10.1016/j.ajog.2010.06.073
Hancock BW, Seckl MJ, Berkowitz RS, editors. Gestational trophoblastic disease. 4th ed. Sheffield: International Society for the Study of Trophoblastic Diseases; 2015. Available from: https://isstd.org/membership-isstd2020/gtd-book
FIGO Oncology Committee. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet. 2002;77(3):285–7. https://doi.org/10.1016/s0020-7292(02)00063-2
Alazzam M, Tidy J, Osborne R, Coleman R, Hancock BW, Lawrie TA. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2012;12(12):CD008891. https://doi.org/10.1002/14651858.CD008891.pub2
Alifrangis C, Agarwal R, Short D, Fisher RA, Sebire NJ, Harvey R, et al. EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol. 2013;31(2):280–6. https://doi.org/10.1200/JCO.2012.43.1817
Lok C, van Trommel N, Massuger L, Golfier F, Seckl M; Clinical Working Party of the EOTTD, et al. Practical clinical guidelines of the EOTTD for treatment and referral of gestational trophoblastic disease. Eur J Cancer. 2020;130:228–40. https://doi.org/10.1016/j.ejca.2020.02.011
Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol. 2009; 112(3):654–62. https://doi.org/10.1016/j.ygyno.2008.09.005
Seidler D, Franklin M. Metastatic choriocarcinoma to the lung: changing dogma. Chest. 2016;150(4):765A. https://doi.org/10.1016/j.chest.2016.08.860
Bakri YN, Berkowitz RS, Khan J, Goldstein DP, von Sinner W, Jabbar FA. Pulmonary metastases of gestational trophoblastic tumor. Risk factors for early respiratory failure. J Reprod Med. mars 1994;39(3):175–8.
Meduri GU, Siemieniuk RAC, Ness RA, Seyler SJ. Prolonged low-dose methylprednisolone treatment is highly effective in reducing duration of mechanical ventilation and mortality in patients with ARDS. J Intensive Care. 2018;6:53. https://doi.org/10.1186/s40560-018-0321-9
Guo Q, Gao J, Guo H, Xie J, Cheng J. Immune checkpoint inhibitor-induced pure red cell aplasia: case series and large-scale pharmacovigilance analysis. Int Immunopharmacol. 2023;114:109490. https://doi.org/10.1016/j.intimp.2022.109490
Suzuki Y, Mobli K, Cass SH, Silva MM, DeAnda A, Tyler DS, et al. Extracorporeal membrane oxygenation for adult patients with neoplasms: outcomes and trend over the last 2 decades. ASAIO J. 2023;69(2):159–66. https://doi.org/10.1097/MAT.0000000000001740
Suzuki Y, Mao RMD, Shah NR, Schaeffer L, Deanda A, Radhakrishnan RS. Prevalence and impact of infection during extracorporeal membrane oxygenation in oncologic patients: a retrospective analysis of the extracorporeal life support organization (elso) registry. J Intensive Care Med. 2023;38(4):391–8. https://doi.org/10.1177/08850666221128243
Tunney R, Scott J, Rudralingam V, Liong S, Athwal VS. Secondary sclerosing cholangitis following extracorporeal membrane oxygenation for acute respiratory distress in polytrauma. Clin Case Rep. 2018;6(9): 1849–53. https://doi.org/10.1002/ccr3.1660
Hatanaka S, Yamada Y, Kubo T, Magara K, Ono Y, Sugita S, et al. Ischemia-induced intestinal de-epithelization and consequent cholangitis lenta after usage of extracorporeal membrane oxygenation in COVID-19 patients: an autopsy series. Oxford Med Case Rep. 2021;2021(3):omab011.
Patel SP, Othus M, Chae YK, Dennis MJ, Gordon S, Mutch D, et al. A Phase II basket trial of dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART SWOG 1609 cohort 47) in patients with gestational trophoblastic neoplasia. Clin Cancer Res. 2024;30(1):33–8. https://doi.org/10.1158/1078-0432.CCR-23-2293
Mangili G, Sabetta G, Cioffi R, Rabaiotti E, Candotti G, Pella F, et al. Current evidence on immunotherapy for gestational trophoblastic neoplasia (GTN). Cancers. 2022;14(11):2782. https://doi.org/10.3390/ cancers14112782
Choi MC, Oh J, Lee C. Effective anti-programmed cell death 1 treatment for chemoresistant gestational trophoblastic neoplasia. Eur J Cancer. 2019;121:94–7. https://doi.org/10.1016/j.ejca.2019.08.024
You B, Bolze PA, Lotz JP, Massardier J, Gladieff L, Joly F, et al. Avelumab in patients with gestational trophoblastic tumors with resistance to single-agent chemotherapy: cohort A of the trophimmun phase II trial. J Clin Oncol. 2020;38(27):3129–37. https://doi.org/10.1200/JCO.20.00803
Goldfarb JA, Dinoi G, Mariani A, Langstraat CL. A case of multi-agent drug resistant choriocarcinoma treated with Pembrolizumab. Gynecol Oncol Rep. 2020;32:100574. https://doi.org/10.1016/j.gore.2020.100574
Clair KH, Gallegos N, Bristow RE. Successful treatment of metastatic refractory gestational choriocarcinoma with pembrolizumab: a case for immune checkpoint salvage therapy in trophoblastic tumors. Gynecol Oncol Rep. 2020;34:100625. https://doi.org/10.1016/j.gore.2020.100625
Paspalj V, Polterauer S, Poetsch N, Reinthaller A, Grimm C, Bartl T. Long-term survival in multiresistant metastatic choriocarcinoma after pembrolizumab treatment: a case report. août. 2021;37:100817. https://doi.org/10.1016/j.gore.2021.100817
Pan W, Hou J. Pembrolizumab for treatment of a male with primary mediastinal choriocarcinoma: a case report. Transl Cancer Res. 2022;11(9):3416–20. https://doi.org/10.21037/tcr-22-766
Niimi K, Yamamoto E, Oda Y, Nishiko Y, Shibata M, Nishino K, et al. A case of complete remission of intractable gestational choriocarcinoma with subsequent chemotherapy after pembrolizumab. Taiwan J Obstet Gynecol. 2023;62(5):745–8. https://doi.org/10.1016/j.tjog.2023.07.019
Kazemi NY, Langstraat C, John Weroha S. Non-gestational choriocarcinoma with hyperprogression on pembrolizumab: a case report and review of the literature. Gynecol Oncol Rep. 2022;39:100923. https://doi.org/10.1016/j.gore.2022.100923
Ghorani E, Kaur B, Fisher RA, Short D, Joneborg U, Carlson JW, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Pembrolizumab is Effective Drug-resistant Gestational Trophoblastic Neoplasia Lancet. 2017;390(10110):2343–5. https://doi.org/10.1016/S0140-6736(17)32894-5
Baas I, Westermann A, You B, Bolze PA, Seckl M, Ghorani E. Immunotherapy for GTN: a new paradigm. Gynecol Obstet Invest. 2023;88(3):194–203.
Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14(1):156. https://doi.org/10.1186/s13045-021-01164-5
Ott PA, Hodi FS, Kaufman HL, Wigginton JM, Wolchok JD. Combination immunotherapy: a road map. J Immunother Cancer. 2017;5(1):16. https://doi.org/10.1186/s40425-017-0218-5
Ling SP, Ming LC, Dhaliwal JS, Gupta M, Ardianto C, Goh KW, et al. Role of immunotherapy in the treatment of cancer: a systematic review. Cancers. 2022;14(21):5205. https://doi.org/10.3390/cancers14215205