Introduction:
Gestational trophoblastic disease (GTD) is a rare group of tumors that starts during pregnancy. These tumors originate in the cells that normally develop into the placenta (an organ that connects the fetus to the uterus). GTD can be non-cancerous (benign) or cancerous (malignant). The tumors typically occur in women under age 20 or over age 40, and it is diagnosed at the early or late stages of childbearing potential. Women who have had a history of GTD tumors are at increased risk of having another. Most GTD tumors can be treated, and the women will be able to become pregnant after treatment and experience a normal pregnancy.
What Is a Gestational Trophoblastic Tumor?
Gestational trophoblastic neoplasia (GTN) is the term to denote a set of malignant placental diseases. It usually develops during the early stages of pregnancy. The choriocarcinoma and invasive mole respond well to chemotherapy. The recovery from the treatment is greater than 90 percent. Usually, chemotherapy works well for GTN. Low-risk GTN is managed with a single agent, like Actinomycin D or Methotrexate, and high-risk GTN should be managed with multiagent chemotherapy, and the regimen usually chosen is EMA-CO, which combines Methotrexate, Etoposide, Actinomycin D, Vincristine, and Cyclophosphamide.
What Is the Treatment for Gestational Trophoblastic Tumors?
Low-Risk Gestational Trophoblastic Tumors:
Low-risk GTN cases are usually treated with one of the single agent Actinomycin D or Methotrexate regimens. Methotrexate is associated with more treatment failure than Actinomycin D. The first-line single-agent chemotherapy regimens for low-risk GTN patients.
- Methotrexate–folinic acid (MTX-FA) eight-day regimen (50 mg of MTX intramuscularly on 1,3,5 and 7th days with Folinic acid 15 mg given orally 24 hours after MTX on two, four, six, and eighth days), this regime is repeated every two weeks.
- Methotrexate (MTX) 0.4 mg/kg intramuscularly or intravenously for five days every two weeks.
- Actinomycin D pulses 1.25 mg/m2 intravenously every two weeks.
- Actinomycin D 0.5 mg intravenously for five days every two weeks.
During chemotherapy treatment, if there has been a positive response to the first agent but if the hCG level plateaus are above normal, then it should be changed to the single alternative agent during treatment. It is also changed when the toxicity prevents the frequency or an adequate dose of treatment. If there is no good response to the single initial agent, then multiple-agent chemotherapy is recommended for high-risk diseases. Multiple-agent chemotherapy is initiated if there is the development of metastasis, a significant elevation in hCG level, or resistance to single-agent chemotherapy.
Many studies have proved that change to single agent Act-D provides a good response rate of between 76 % to 87 % in patients with low hCG levels. Clinicopathologic diagnosis of choriocarcinoma and higher WHO risk score (5 to 6) are both associated with a high risk of resistance to single-agent chemotherapy. To reduce this, lowering the threshold for multiple-agent chemotherapy use in low-risk patients can be considered. When the hCG level returns to normal, two to three more cycles of chemotherapy will reduce the chance of recurrence.
High-Risk Gestational Trophoblastic Tumors:
Multiple-agent chemotherapy regimens are commonly used to treat high-risk GTN. EMA-CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Vincristine). About 20 percent of patients fail EMA-CO therapy, but most can be recovered with further therapy. However, the overall survival rates for high-risk GTN patients are as high as 95 percent. In patients with poor outcomes, there will be numerous adverse features that include liver and brain metastasis.
EMA-CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Vincristine) chemotherapy regime is as follows:
Regime 1:
Day One -
- Etoposide - 100 mg/m2 IV infusion over 30 minutes.
- Actinomycin D - 0.5 mg IV bolus.
- Methotrexate - 100 mg/m2 IV bolus or 200 mg/m2 IV infusion over 12 hours.
Day Two -
- Etoposide - 100 mg/m2 IV infusion over 30 minutes.
- Actinomycin D - 0.5 mg IV bolus.
- Folinic Acid Rescue - 15 mg orally or intramuscularly every 12 hours for four doses.
Regime 2:
- Vincristine - 1 mg/m2 IV bolus (maximum 2 mg).
- Cyclophosphamide - 600 mg/m2 IV infusion over 30 minutes.
The two regimes are followed alternatively every two weeks.
Ultra High-Risk Gestational Trophoblastic Tumors:
Among the high-risk group, a subgroup with a score of 13 or greater, and patients with brain, liver, or extensive metastases, respond to the first-line multiple-agent chemotherapy treatments poorly.
For people with the massive disease, when the treatment is started with standard chemotherapy, it may lead to sudden tumor collapse with severe bleeding, myelosuppression, septicemia, metabolic acidosis, and multiple organ failure, which can result in early death. To avoid these consequences, initially, gentle chemotherapy is started rather than full-dose chemotherapy. Induction of Etoposide 100 mg/m2 and Cisplatin 20 mg/m2 on days one and two, for one to three weeks, before initiation of normal chemotherapy may eliminate early deaths with promising results.
For those patients with brain or liver metastases, a very high-risk score, EP (Etoposide and Platinum), and EMA or other more severe chemotherapy regimens may provide a better outcome and response.
Surgery - Surgery plays an important role in the treatment of GTN. Hysterectomy may be suggested to treat uncontrolled uterine bleeding, but it can be avoided with the use of uterine artery embolization. To stop bleeding in organs such as the gastrointestinal tract, kidneys, liver, and spleen, a laparotomy may be needed. In some cases, neurosurgery is required if there is bleeding into the brain or high intracranial pressure.
Radiotherapy - Radiotherapy has a very limited role in GTN treatment, except in the treatment of brain metastasis.
What Is the Follow-up for the GTN Tumor?
After the treatment of GTN, hCG monitoring is required every month for at least 12 months. The hCG monitoring is essential for the surveillance of relapse. And throughout the duration, any reliable contraception must be used. Further pregnancy, offspring, and fertility are not affected after the procedure. However, sexual and psychosocial counseling may be required for some patients.
Conclusion:
Gestational trophoblastic tumors are a group of rare tumors that develop from abnormal growth of the cells that normally form the placenta during pregnancy. Various treatment options are available for these tumors, including surgery, chemotherapy, and radiation therapy. The treatment protocol for gestational trophoblastic tumors depends on a number of factors, including the type and stage of the tumor, as well as the patient's overall health. With appropriate treatment, the majority of patients with gestational trophoblastic tumors can be successfully cured, and many can go on to have healthy pregnancies in the future.
