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User:SKXu/Gestational choriocarcinoma

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Notes for order:

Disease/disorder/syndrome

  • signs/symptoms
  • causes
  • mechanisms
  • diagnosis
  • screening
  • TX
  • prognosis
  • research?
  • special populations

Current article:

Gestational choriocarcinoma is a malignant trophoblastic tumour arising from any gestational event during pregnancy in the reproductive female. Women with gestational choriocarcinoma may present with abnormal vaginal bleeding, persistent markedly elevated βhCG, or a history of prior pregnancy. Development of gestational choriocarcinoma commonly occurs shortly after gestational anomalies, but pathology may occur after a long latency of years. It may occur during pregnancy. Often, gestational choriocarcinoma happens after a growth of some sort in the womb (pregnancy, tumor, mole, cyst)[1]

  • note: "reproductive female" should likely be removed (DEI)

Gestational choriocarcinoma is a type of gestational trophoblastic neoplasia that can occur during pregnancy. It is a rare disease that can occur mainly in or after molar pregnancies, where abnormal trophoblast developments leads to trophoblastic tumors. The choriocarcinoma can metastasize to other organs, including the lungs, kidney, and liver.[2]

Those with gestational choriocarcinoma may experience abnormal vaginal bleeding, abdominal pain, and have high levels of hCG, in addition to history of molar pregnancy or other metastatic cancer.[2] Guidelines from the Federation of Gynecologists and Obstetricians (FIGO) exist to evaluate risk and treatment of the disease.[3]

  • need to double check if this pulls from FIGO or is specifically for Canada

(malignant [gestational trophoblastic] tumors - abnormal production of trophoblastic tissue)

Cause

[edit]

Diagnosis

[edit]

Common characteristic manifestation of gestational choriocarcinoma include irregular vaginal bleeding and hydatidiform moles. A hydatidiform mole is a red hemorrhagic mass with various sizes in the uterus. Often, diagnosis is presumptive. It is based on clinical findings and the identification of a malignant trophoblast. One prevalent symptom is vaginal bleeding after a pregnancy, abortion, or hydatidiform mole.[4] A pregnancy test will be positive even if there is no embryo/fetus.[5]

A differential diagnosis for gestational choriocarcinoma usually happens at a late clinical stage, and this is partly due to the wide spectrum and rare clinical presentations of the disease.[6] Individuals presented with the disease are mostly in their reproductive years. (CITE from existing link)

Similar to other non-gestational tumors, gestational choriocarcinoma can be reflected via an elevated level in serum hCG concentration[7]. Besides the change in serum hCG levels, the diagnosis of gestational choriocarcinoma also focuses on the presence of metastases after any types of pregnancy events.[8] Based on FIGO's updated guidelines on gestational trophoblastic disease management, the diagnostic criteria of a post-gestational trophoblastic neoplasia (GTN) is as follows:[9]

  1. Over a period of 3 weeks or longer (day 1, 7, 14, 21), there are 4 or more plateaued hCG levels.
  2. Over a period of 2 weeks or longer (day 1, 7, 14), there are 3 consecutive weekly measurements of rising hCG levels.
  3. A histological diagnosis of choriocarcinoma.

There are currently different guidelines available in terms of diagnosing and recommending treatment options for gestational trophoblastic neoplasia (GTN). The 4 guidelines identified are: the Royal College of Obstetricians and Gynecologists (RCOG), the International Federation of Gynecology and Obstetrics (FIGO), the European Society for Medical Oncology (ESMO), and the Royal Australian and New Zealand College of Obstetricians and Gynecologists (RANZCOG). The differences in GTN diagnosis between the guidelines are as follows:[10]

Comparison chart of available guidelines on gestational trophoblastic neoplasia (GTN) diagnosis
RCOG ESMO FIGO RANZCOG
Clinical presentation x x
FIGO Criteria (*see above) x x x x
Urine hCG level x
Post-molar hCG level x x

To differentiate gestational choriocarcinoma from other tumors such as lung or brain cancers, a genetic test is usually completed on top of a pathological diagnosis.[7] DNA genotyping is a powerful tool that helps with the differentiation. The technique can accurately determine the time that it takes to develop the observed tumor and the type of index gestation, which includes term pregnancy, molar gestation, or non-molar abortion.[11]

Treatment

[edit]

Chemotherapy is the first line treatment for this disease due to the susceptability of choriocarcinomas to this treatment option.[12][13] Chemotherapy treatment includes platinum-based therapy, Taxol, and a Taxol and carboplatin combination. Other types of treatment include hysterectomy and radiation, although these are very rarely.[14]

Given the nature of this disease, chemo-resistance could develop and lead to disease relapse. A recent systemic treatment review, it has anticipated that anti-PD1/PD-L1 checkpoint inhibitor would play a significant role in the management of relapsed gestational trophoblastic disease.

Due to the susceptability of choriocarcinomas to chemotherapy, it is the first line treatment for this disease. Treatment course depends on the FIGO Scoring System for GTN, which has various prognostic factors, and categorizes based on low risk with a score of 0-6 and high risk with a score of 7 and above. Individuals with low risk GTN are usually treated with single agent chemotherapy, such as methotrexate and folinic acid (MTX/FA) or actinomycin D (ActD) for 3 cycles.[15] Other treatment options for individuals with low risk include hysterectomy and surgical removal of the tumor if possible. Those with high risk GTN receive a multi-agent chemotherapy regimen, usually consisting of a weekly rotation of etopside, methotrexate, and actinomycin D given one week and cyclophosphamide and vincristine given the following week (EMA-CO), with variations to treatment occuring on a patient-specific basis. In individuals who relapse, secondary chemotherapy is needed where treatment may vary from the original regimen. The treatment includes a platinum-etopside combination given with other chemotherapy medications, such as methotrexate and actinomycin D (EMA-EP), bleomycin (BEP), or ifosfamide (VIP, ICE).[16] Additional treatment also consists of surgery and radiotherapy if deemed appropriate for the individual.[17] This condition can also result in resistance to the medications used to treat it and failure of their success in the individuals.[18] If this occurs, individuals usually undergo a more intensive medication regimen than what was originally given to them.[19] New treatment options designed to reduce the risk of resistance are currently being researched, such as immune checkpoint inhibitors.[20]

Studies of gestational choriocarcinoma demonstrate an increased expression of the ligand PD-L1 and its corresponding receptor PD-1, leading to drug research and development into medications that can block the PD-1 receptor, such as Pembrolizumab.[21] In individuals requiring more intensive chemotherapy options, using an immune checkpoint inhibitor may be preferable to long-term use of multi-agent chemotherapy to prevent prolonged toxicity to the body.[22]

Gestational choriocarcinoma can also cause metastasis in various parts of the body, usually occuring in the lungs.[23]

  • phrasing of "cases" was changed
  • added source for chemotherapy, need to do more reading on this
  • remove "other types..." because NIH citation
FIGO Scoring System for GTN
Prognostic Factor 0 1 2 4
Age <40 ≥40 - -
Previous Pregnancy Hydatidiform mole Abortion Term
Months since last pregnancy Less than 4 4 to 6 7-12 >12
Pre-treatment hCG (IU/mL) <103 103 to 104 >104 to 105 >105
Largest tumor size, including uterus <3cm 3-4 cm ≥5cm -
Site of spread Lung Spleen or kidney GI Tract Brain, liver
Number of metastases - 1 to 4 5-8 >8
Previous Failed chemotherapy - - Single Drug ≥2

Prognosis

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At the time of diagnosis, more than 90% of patients already have lung metastases, though there are also less frequent metastases to the brain and liver. With chemotherapy, there is an 80% 5-year survival rate. Ultimately, death is related to liver and brain metastases.

The survival rate following treatment with chemotherapy is approximately 90%.[24] Overall survival rate is also higher when management of gestational choriocarcinoma occurs in a setting with physicians familiar with the condition.[17]

  1. ^ NIH. "Choriocarcinoma". Retrieved 10 August 2012.
  2. ^ Sharami, Seyedeh Reyhaneh Yousefi; Saffarieh, Elham (2020). "A review on management of gestational trophoblastic neoplasia". Journal of Family Medicine and Primary Care. 9 (3): 1287–1295. doi:10.4103/jfmpc.jfmpc_876_19. ISSN 2249-4863. PMC 7266251. PMID 32509606.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Eiriksson, Lua; Dean, Erin; Sebastianelli, Alexandra; Salvador, Shannon; Comeau, Robyn; Jang, Ji-Hyun; Bouchard-Fortier, Geneviève; Osborne, Ray; Sauthier, Philippe (2021-01-01). "Guideline No. 408: Management of Gestational Trophoblastic Diseases". Journal of Obstetrics and Gynaecology Canada. 43 (1): 91–105.e1. doi:10.1016/j.jogc.2020.03.001. ISSN 1701-2163. PMID 33384141.
  4. ^ NIH. "Choriocarcinoma". Retrieved 10 August 2012.
  5. ^ NIH. "Choriocarcinoma". Retrieved 10 August 2012.
  6. ^ Mangla, Mishu; Singla, Deepak; Kaur, Harpreet; Sharma, Sushmita (2017-02-01). "Unusual clinical presentations of choriocarcinoma: A systematic review of case reports". Taiwanese Journal of Obstetrics and Gynecology. 56 (1): 1–8. doi:10.1016/j.tjog.2015.05.011. ISSN 1028-4559.
  7. ^ a b Lok, Christianne; Frijstein, Minke; van Trommel, Nienke (2021). "Clinical presentation and diagnosis of Gestational Trophoblastic Disease". Best Practice & Research Clinical Obstetrics & Gynaecology. 74: 42–52. doi:10.1016/j.bpobgyn.2020.12.001.
  8. ^ Lurain, John R. (2010). "Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole". American Journal of Obstetrics & Gynecology. 203 (6): 531–539. doi:10.1016/j.ajog.2010.06.073. ISSN 0002-9378.
  9. ^ Ngan, Hextan Y.S.; Seckl, Michael J.; Berkowitz, Ross S.; Xiang, Yang; Golfier, François; Sekharan, Paradan K.; Lurain, John R.; Massuger, Leon (2018). "Update on the diagnosis and management of gestational trophoblastic disease". International Journal of Gynecology & Obstetrics. 143: 79–85. doi:10.1002/ijgo.12615.
  10. ^ Tsakiridis, Ioannis; Giouleka, Sonia; Kalogiannidis, Ioannis; Mamopoulos, Apostolos; Athanasiadis, Apostolos; Dagklis, Themistoklis (2020). "Diagnosis and Management of Gestational Trophoblastic Disease: A Comparative Review of National and International Guidelines". Obstetrical & Gynecological Survey. 75 (12): 747–756. doi:10.1097/OGX.0000000000000848. ISSN 1533-9866.
  11. ^ Buza, Natalia; Hui, Pei (2021). "Genotyping diagnosis of gestational trophoblastic disease: frontiers in precision medicine". Modern Pathology. 34 (9): 1658–1672. doi:10.1038/s41379-021-00831-9. ISSN 0893-3952.
  12. ^ Seckl, M. J.; Sebire, N. J.; Fisher, R. A.; Golfier, F.; Massuger, L.; Sessa, C. (2013). "Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†". Annals of Oncology. 24: vi39–vi50. doi:10.1093/annonc/mdt345. ISSN 0923-7534.
  13. ^ Clark, James; Slater, Susanna; Seckl, Michael J (2021-02-01). "Treatment of Gestational Trophoblastic Disease in the 2020s". Current opinion in obstetrics & gynecology. 33 (1): 7–12. doi:10.1097/GCO.0000000000000674. ISSN 1040-872X. PMC 7116872. PMID 33337613.
  14. ^ NIH. "Choriocarcinoma". Retrieved 10 August 2012.
  15. ^ Braga, Antonio; Mora, Paulo; de Melo, Andréia Cristina; Nogueira-Rodrigues, Angélica; Amim-Junior, Joffre; Rezende-Filho, Jorge; Seckl, Michael J (2019-02-24). "Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide". World Journal of Clinical Oncology. 10 (2): 28–37. doi:10.5306/wjco.v10.i2.28. ISSN 2218-4333. PMC 6390119. PMID 30815369.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  16. ^ "Secondary chemotherapy for high-risk gestational trophoblastic neoplasia". Gynecologic Oncology. 97 (2): 618–623. 2005-05-01. doi:10.1016/j.ygyno.2005.02.004. ISSN 0090-8258.
  17. ^ a b Braga, Antonio; Mora, Paulo; de Melo, Andréia Cristina; Nogueira-Rodrigues, Angélica; Amim-Junior, Joffre; Rezende-Filho, Jorge; Seckl, Michael J (2019). "Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide". World Journal of Clinical Oncology. 10 (2): 28–37. doi:10.5306/wjco.v10.i2.28. ISSN 2218-4333. PMC 6390119. PMID 30815369.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ Winter, Matthew C. (2021-07). "Treatment of low-risk gestational trophoblastic neoplasia". Best Practice & Research. Clinical Obstetrics & Gynaecology. 74: 67–80. doi:10.1016/j.bpobgyn.2021.01.006. ISSN 1532-1932. PMID 33741258. {{cite journal}}: Check date values in: |date= (help)
  19. ^ Winter, Matthew C. (2021-07). "Treatment of low-risk gestational trophoblastic neoplasia". Best Practice & Research. Clinical Obstetrics & Gynaecology. 74: 67–80. doi:10.1016/j.bpobgyn.2021.01.006. ISSN 1532-1932. PMID 33741258. {{cite journal}}: Check date values in: |date= (help)
  20. ^ Winter, Matthew C. (2021-07). "Treatment of low-risk gestational trophoblastic neoplasia". Best Practice & Research. Clinical Obstetrics & Gynaecology. 74: 67–80. doi:10.1016/j.bpobgyn.2021.01.006. ISSN 1532-1932. PMID 33741258. {{cite journal}}: Check date values in: |date= (help)
  21. ^ Braga, Antonio; Mora, Paulo; de Melo, Andréia Cristina; Nogueira-Rodrigues, Angélica; Amim-Junior, Joffre; Rezende-Filho, Jorge; Seckl, Michael J (2019-02-24). "Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide". World Journal of Clinical Oncology. 10 (2): 28–37. doi:10.5306/wjco.v10.i2.28. ISSN 2218-4333. PMC 6390119. PMID 30815369.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Braga, Antonio; Mora, Paulo; de Melo, Andréia Cristina; Nogueira-Rodrigues, Angélica; Amim-Junior, Joffre; Rezende-Filho, Jorge; Seckl, Michael J (2019-02-24). "Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide". World Journal of Clinical Oncology. 10 (2): 28–37. doi:10.5306/wjco.v10.i2.28. ISSN 2218-4333. PMC 6390119. PMID 30815369.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  23. ^ Ma, Dongjie; Zhang, Zhiyong; Li, Shanqing (2011-10). "[Progress of the diagnosis and treatment of pulmonary metastasis of gestational choriocarcinoma]". Zhongguo Fei Ai Za Zhi = Chinese Journal of Lung Cancer. 14 (10): 801–805. doi:10.3779/j.issn.1009-3419.2011.10.06. ISSN 1999-6187. PMC 5999937. PMID 22008110. {{cite journal}}: Check date values in: |date= (help)
  24. ^ Ngan, Hextan Y.S.; Seckl, Michael J.; Berkowitz, Ross S.; Xiang, Yang; Golfier, François; Sekharan, Paradan K.; Lurain, John R.; Massuger, Leon (2018). "Update on the diagnosis and management of gestational trophoblastic disease". International Journal of Gynecology & Obstetrics. 143: 79–85. doi:10.1002/ijgo.12615.
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