Materiały źródłowe

• #1 Persistent trophoblastic disease and choriocarcinoma | nidirect

  https://www.nidirect.gov.uk/conditions/persistent-trophoblastic-disease-and-choriocarcinoma

  Persistent trophoblastic disease and choriocarcinoma are very rare pregnancy-related tumours. They are known as gestational trophoblastic tumours (GTTs). […] Chemotherapy is usually used to treat the condition. Treatment is successful in curing almost all cases of persistent trophoblastic disease. […] Chemotherapy is used to treat choriocarcinoma and usually successfully cures it. […] Overall, the outlook for persistent trophoblastic disease and choriocarcinoma is excellent. 98 to 100 per cent of women who develop a gestational trophoblastic cancer are cured.

• #2 Persistent Trophoblastic Disease: Causes, Treatment, Benefit

  https://drgalen.org/medical-treatment/persistent-trophoblastic-disease-and-choriocarcinoma

  Persistent Trophoblastic Disease (PTD) and Choriocarcinoma are rare forms of gestational trophoblastic neoplasia (GTN), originating from abnormal placental tissue. […] Timely diagnosis involves imaging, blood tests, and sometimes biopsy, leading to treatment strategies comprising chemotherapy and surgery. […] Addressing Persistent Trophoblastic Disease and Choriocarcinoma requires a comprehensive and multidisciplinary approach. The primary modalities of treatment include chemotherapy, surgery, and close monitoring of the patient’s condition. […] Chemotherapy plays a pivotal role in the treatment of both Persistent Trophoblastic Disease and Choriocarcinoma. The use of potent drugs aims to eradicate cancer cells throughout the body. […] Surgical intervention may be considered, especially when tumors are localized or when the disease does not respond adequately to chemotherapy alone.

• #3 Persistent trophoblastic disease and choriocarcinoma | nidirect

  https://www.nidirect.gov.uk/conditions/persistent-trophoblastic-disease-and-choriocarcinoma

  Persistent trophoblastic disease and choriocarcinoma are very rare pregnancy-related tumours. They are known as gestational trophoblastic tumours (GTTs). […] Chemotherapy is usually used to treat the condition. Treatment is successful in curing almost all cases of persistent trophoblastic disease. […] Chemotherapy is used to treat choriocarcinoma and usually successfully cures it. […] Overall, the outlook for persistent trophoblastic disease and choriocarcinoma is excellent. 98 to 100 per cent of women who develop a gestational trophoblastic cancer are cured.

• #4 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. […] The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM (tumor, node, metastasis) staging system has limited prognostic value. […] Selection of treatment depends on these factors plus the patients desire for future pregnancies. Beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.

• #5 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. […] The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM (tumor, node, metastasis) staging system has limited prognostic value. […] Selection of treatment depends on these factors plus the patients desire for future pregnancies. Beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.

• #6 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers), A tissue diagnosis of choriocarcinoma, A plateau of the beta-hCG for 3 weeks, Persistence of detectable beta-hCG 6 months after mole evacuation, Metastatic disease, An elevation in beta-hCG after a normal value, Postevacuation hemorrhage not caused by retained tissues.

• #7 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.gestational-trophoblastic-disease-treatment-pdq%C2%AE-treatment-health-professional-information-nci.ncicdr0000062901

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers). A tissue diagnosis of choriocarcinoma. A plateau of the beta-hCG for 3 weeks. Persistence of detectable beta-hCG 6 months after mole evacuation. Metastatic disease. An elevation in beta-hCG after a normal value. Postevacuation hemorrhage not caused by retained tissues.

• #8 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI]

  https://awog.org/womens-health/health-library?DOCHWID=ncicdr0000062901

  Most hydatidiform moles (HMs) are benign and are treated conservatively by dilation, suction evacuation, and curettage. However, since they carry a risk of persistence or progression to malignant gestational trophoblastic disease (GTD), they must be followed carefully with weekly serum human chorionic gonadotropin (hCG) levels to normalization. […] Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers). A tissue diagnosis of choriocarcinoma. A plateau of the beta-hCG for 3 weeks. Persistence of detectable beta-hCG 6 months after mole evacuation. Metastatic disease. An elevation in beta-hCG after a normal value. Postevacuation hemorrhage not caused by retained tissues.

• #9 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers), A tissue diagnosis of choriocarcinoma, A plateau of the beta-hCG for 3 weeks, Persistence of detectable beta-hCG 6 months after mole evacuation, Metastatic disease, An elevation in beta-hCG after a normal value, Postevacuation hemorrhage not caused by retained tissues.

• #10 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.gestational-trophoblastic-disease-treatment-pdq%C2%AE-treatment-health-professional-information-nci.ncicdr0000062901

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers). A tissue diagnosis of choriocarcinoma. A plateau of the beta-hCG for 3 weeks. Persistence of detectable beta-hCG 6 months after mole evacuation. Metastatic disease. An elevation in beta-hCG after a normal value. Postevacuation hemorrhage not caused by retained tissues.

• #11 Gestational Trophoblastic Disease | Doctor

  https://patient.info/doctor/gestational-trophoblastic-disease

  Indications for chemotherapy in GTD […] Plateaued or rising hCG levels after evacuation. […] Histological evidence of choriocarcinoma. […] Evidence of metastases in the brain, liver, or gastrointestinal (GI) tract, or radiological opacities 2 cm on CXR. […] Pulmonary, vulval, or vaginal metastases unless hCG concentrations are falling. […] Heavy vaginal bleeding or evidence of GI or intraperitoneal haemorrhage. […] Serum hCG greater than 20,000 IU/L more than four weeks after evacuation, because of the risk of uterine perforation with further evacuation attempts. […] Raised hCG level six months after evacuation (even if falling). […] Chemotherapy regimes […] Women with evidence of persistent GTD should undergo assessment of their disease followed by chemotherapy. Treatment used is based on the International Federation of Gynecology and Obstetrics (FIGO) 2000 scoring system for GTN following assessment at the treatment centre. […] Women with GTN may be treated with single-agent or multi-agent chemotherapy. […] PSTT and ETT are now recognised as variants of GTN. They may be treated with surgery because they are less sensitive to chemotherapy. […] Women with FIGO scores of 6 or less are at low risk and are treated with single-agent intramuscular methotrexate, alternating daily with folinic acid for one week followed by six rest days. […] Women with scores of 7 or greater are at high risk and are treated with intravenous multi-agent chemotherapy, which includes combinations of methotrexate, dactinomycin, etoposide, cyclophosphamide and vincristine. […] Treatment is continued, in all cases, until the hCG level has returned to normal and then for a further six consecutive weeks. […] Women suspected of choriocarcinoma require more extensive investigation in the specialist centre, including computerised tomography of the chest and abdomen, or magnetic resonance imaging of the head and pelvis, all with contrast in addition to the serum hCG and a Doppler ultrasound of the pelvis. […] Any woman with a score of 13 or greater is now recognised to have a higher risk of early death (within four weeks), often due to bleeding into organs, or late death due to multihyphenate drug-resistant disease. […] Rarely, women with multi-relapsed disease will require high-dose chemotherapy with stem cell recovery.

• #12 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI]

  https://awog.org/womens-health/health-library?DOCHWID=ncicdr0000062901

  Most hydatidiform moles (HMs) are benign and are treated conservatively by dilation, suction evacuation, and curettage. However, since they carry a risk of persistence or progression to malignant gestational trophoblastic disease (GTD), they must be followed carefully with weekly serum human chorionic gonadotropin (hCG) levels to normalization. […] Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers). A tissue diagnosis of choriocarcinoma. A plateau of the beta-hCG for 3 weeks. Persistence of detectable beta-hCG 6 months after mole evacuation. Metastatic disease. An elevation in beta-hCG after a normal value. Postevacuation hemorrhage not caused by retained tissues.

• #13 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers), A tissue diagnosis of choriocarcinoma, A plateau of the beta-hCG for 3 weeks, Persistence of detectable beta-hCG 6 months after mole evacuation, Metastatic disease, An elevation in beta-hCG after a normal value, Postevacuation hemorrhage not caused by retained tissues.

• #14 Advances in the diagnosis and early management of gestational trophoblastic disease | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000321

  The treatment of invasive mole and choriocarcinoma is often initiated on the basis of a rising hCG level even in the absence of other clinical evidence of disease recurrence. […] Women with invasive mole or choriocarcinoma are stratified into low or high risk GTN categories based on the Federation of Gynaecology and Obstetrics (FIGO) staging and modified WHO prognostic scoring system. […] Women with low risk disease (score of 6) without metastatic disease are offered single drug chemotherapy or hysterectomy. Whereas women with high risk disease (score of 7) are offered multidrug chemotherapy, ideally under the supervision of an expert in GTD management. […] Use of checkpoint inhibitor immunotherapy (eg, pembrolizumab) for chemoresistant, very high risk GTN has had some success. […] Hence, clinical trials are evaluating the use of checkpoint inhibitors alone or in combination with chemotherapy to target choriocarcinoma.

• #15

  https://journals.lww.com/greenjournal/fulltext/2021/02000/gestational_trophoblastic_disease__current.22.aspx

  The most frequently used single-agent regimens with methotrexate and actinomycin D are listed in Table 4. […] Patients with a FIGO risk score of 7 or higher should initially be treated with aggressive multiagent chemotherapy; surgery or radiation or both are often incorporated into treatment. […] Multiagent regimens incorporate etoposide, with or without cisplatin, into cyclical combination chemotherapy with high rates of success and lower acute toxicity. […] Treatment of high-risk gestational trophoblastic neoplasia that is resistant to initial chemotherapy is challenging. […] Chemotherapy is continued until hCG values have normalized, and this is followed by at least two to three courses of consolidation chemotherapy for the purpose of eradicating all viable tumor. […] After hCG remission has been achieved, patients with gestational trophoblastic neoplasia should be managed with serial determinations of hCG levels at 2-week intervals during the first 3 months of remission and then at monthly intervals for at least 12 months.

• #16 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] – Health Information Library | PeaceHealth

  https://www.peacehealth.org/medical-topics/id/ncicdr0000062901

  Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. […] The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM (tumor, node, metastasis) staging system has limited prognostic value. The probability of cure depends on the following: Histological type (invasive mole or choriocarcinoma), extent of spread of the disease/largest tumor size, level of serum beta-hCG, duration of disease from the initial pregnancy event to start of treatment, number and specific sites of metastases, nature of antecedent pregnancy, and extent of prior treatment. […] Selection of treatment depends on these factors plus the patient’s desire for future pregnancies. Beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.

• #17 Gestational Trophoblastic Disease Treatment – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/patient/gtd-treatment-pdq

  Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease (GTD) that is almost always malignant. […] A choriocarcinoma is a malignant tumor that forms from trophoblast cells and spreads to the muscle layer of the uterus and nearby blood vessels. […] The treatment of gestational trophoblastic neoplasia is based on the type of disease, stage, or risk group. […] Invasive moles and choriocarcinomas are treated based on risk groups. […] Treatment options also depend on whether the woman wishes to become pregnant in the future. […] There are different types of treatment for patients with gestational trophoblastic disease. […] Three types of standard treatment are used: Surgery, Chemotherapy, Radiation therapy. […] After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy after surgery to kill any cancer cells that are left.

• #18 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. […] The prognosis for cure of patients with GTDs is good even when the disease has spread to distant organs, especially when only the lungs are involved. Therefore, the traditional TNM (tumor, node, metastasis) staging system has limited prognostic value. […] Selection of treatment depends on these factors plus the patients desire for future pregnancies. Beta-hCG is a sensitive marker to indicate the presence or absence of disease before, during, and after treatment. Given the extremely good therapeutic outcomes of most of these tumors, an important goal is to distinguish patients who need less-intensive therapies from those who require more-intensive regimens to achieve a cure.

• #19 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with GTN are subdivided into 2 groups: those with a WHO score of less than 7 (low-risk) and those with a score of 7 or higher and who are at high risk of therapy failure. Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy, as follows: Methotrexate is preferred by many US specialists, but actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. Six weeks of maintenance chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the serum hCG levels rise or plateau and the WHO score remains less than 7. […] Treatment in patients with WHO scores of 7 or higher is as follows: EMA-CO regimen A combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle, and cyclophosphamide and vincristine (Oncovin) administered in the second week. EMA-EP regimen Cisplatin and etoposide are substituted for cyclophosphamide and vincristine during the second week; sometimes reserved for patients in whom EMA-CO fails. At least 6 weeks of maintenance EMA-CO or EMA-EP are administered after a normal serum hCG level. Patients with liver metastasis are considered for liver irradiation (2000 cGy).

• #20 Advances in the diagnosis and early management of gestational trophoblastic disease | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000321

  The treatment of invasive mole and choriocarcinoma is often initiated on the basis of a rising hCG level even in the absence of other clinical evidence of disease recurrence. […] Women with invasive mole or choriocarcinoma are stratified into low or high risk GTN categories based on the Federation of Gynaecology and Obstetrics (FIGO) staging and modified WHO prognostic scoring system. […] Women with low risk disease (score of 6) without metastatic disease are offered single drug chemotherapy or hysterectomy. Whereas women with high risk disease (score of 7) are offered multidrug chemotherapy, ideally under the supervision of an expert in GTD management. […] Use of checkpoint inhibitor immunotherapy (eg, pembrolizumab) for chemoresistant, very high risk GTN has had some success. […] Hence, clinical trials are evaluating the use of checkpoint inhibitors alone or in combination with chemotherapy to target choriocarcinoma.

• #21 Cancer drug treatment for invasive mole and choriocarcinoma | Gestational trophoblastic disease (GTD) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/gestational-trophoblastic-disease-gtd/invasive-mole-choriocarcinoma/treatment/cancer-drug-treatment

  Chemotherapy is the most common treatment for an invasive mole or choriocarcinoma. […] The main treatment for invasive mole or choriocarcinoma is chemotherapy. But some women might be offered surgery. […] You usually have treatment with methotrexate if you have low risk disease. You have it as an injection into a muscle (intramuscularly) every other day for a week. […] If your hCG levels don’t go back down to normal or they begin to go up again, it is known as methotrexate resistance. You will change chemotherapy. […] If you have a high risk invasive mole or choriocarcinoma, you usually have a combination of chemotherapy drugs. […] If your risk score is over 13, you might have a lower dose of chemotherapy to start with. This is to lower the risk of serious side effects. This is called induction chemotherapy.

• #22 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with GTN are subdivided into 2 groups: those with a WHO score of less than 7 (low-risk) and those with a score of 7 or higher and who are at high risk of therapy failure. Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy, as follows: Methotrexate is preferred by many US specialists, but actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. Six weeks of maintenance chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the serum hCG levels rise or plateau and the WHO score remains less than 7. […] Treatment in patients with WHO scores of 7 or higher is as follows: EMA-CO regimen A combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle, and cyclophosphamide and vincristine (Oncovin) administered in the second week. EMA-EP regimen Cisplatin and etoposide are substituted for cyclophosphamide and vincristine during the second week; sometimes reserved for patients in whom EMA-CO fails. At least 6 weeks of maintenance EMA-CO or EMA-EP are administered after a normal serum hCG level. Patients with liver metastasis are considered for liver irradiation (2000 cGy).

• #23 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2395266/

  The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. […] Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility. […] Low-dose methotrexate with folinic acid rescue, as described by Bagshawe et al, (1989), has been the standard treatment for low-risk disease at the Sheffield Trophoblastic Tumour Centre for many years. […] Patients were continued on chemotherapy for 68 weeks after reaching complete remission (CR); that is, a normal serum hCG. […] The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy.

• #24 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2395266/

  The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. […] Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility. […] Low-dose methotrexate with folinic acid rescue, as described by Bagshawe et al, (1989), has been the standard treatment for low-risk disease at the Sheffield Trophoblastic Tumour Centre for many years. […] Patients were continued on chemotherapy for 68 weeks after reaching complete remission (CR); that is, a normal serum hCG. […] The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy.

• #25 Cancer drug treatment for invasive mole and choriocarcinoma | Gestational trophoblastic disease (GTD) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/gestational-trophoblastic-disease-gtd/invasive-mole-choriocarcinoma/treatment/cancer-drug-treatment

  Chemotherapy is the most common treatment for an invasive mole or choriocarcinoma. […] The main treatment for invasive mole or choriocarcinoma is chemotherapy. But some women might be offered surgery. […] You usually have treatment with methotrexate if you have low risk disease. You have it as an injection into a muscle (intramuscularly) every other day for a week. […] If your hCG levels don’t go back down to normal or they begin to go up again, it is known as methotrexate resistance. You will change chemotherapy. […] If you have a high risk invasive mole or choriocarcinoma, you usually have a combination of chemotherapy drugs. […] If your risk score is over 13, you might have a lower dose of chemotherapy to start with. This is to lower the risk of serious side effects. This is called induction chemotherapy.

• #26 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2395266/

  The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. […] Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility. […] Low-dose methotrexate with folinic acid rescue, as described by Bagshawe et al, (1989), has been the standard treatment for low-risk disease at the Sheffield Trophoblastic Tumour Centre for many years. […] Patients were continued on chemotherapy for 68 weeks after reaching complete remission (CR); that is, a normal serum hCG. […] The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy.

• #27 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2395266/

  The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. […] Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility. […] Low-dose methotrexate with folinic acid rescue, as described by Bagshawe et al, (1989), has been the standard treatment for low-risk disease at the Sheffield Trophoblastic Tumour Centre for many years. […] Patients were continued on chemotherapy for 68 weeks after reaching complete remission (CR); that is, a normal serum hCG. […] The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy.

• #28 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects | British Journal of Cancer

  https://www.nature.com/articles/6601422

  The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. […] Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility. […] Low-dose methotrexate with folinic acid rescue, as described by Bagshawe et al, (1989), has been the standard treatment for low-risk disease at the Sheffield Trophoblastic Tumour Centre for many years. […] For all patients, the initial CR rate of 72% and overall 99% cure rate justifies the strategy of treating all low-/medium-risk patients initially with single-agent methotrexate in the knowledge that almost all who are resistant to this first-line therapy can be salvaged with alternative or more intensive regimens. […] In conclusion, methotrexate achieves high CR rates for low-risk persistent gestational trophoblastic disease. There are several different protocols for treatment administration, but larger comparative studies of their efficacy and toxicity, as well as long-term outcome are needed.

• #29 Cancer drug treatment for invasive mole and choriocarcinoma | Gestational trophoblastic disease (GTD) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/gestational-trophoblastic-disease-gtd/invasive-mole-choriocarcinoma/treatment/cancer-drug-treatment

  Chemotherapy is the most common treatment for an invasive mole or choriocarcinoma. […] The main treatment for invasive mole or choriocarcinoma is chemotherapy. But some women might be offered surgery. […] You usually have treatment with methotrexate if you have low risk disease. You have it as an injection into a muscle (intramuscularly) every other day for a week. […] If your hCG levels don’t go back down to normal or they begin to go up again, it is known as methotrexate resistance. You will change chemotherapy. […] If you have a high risk invasive mole or choriocarcinoma, you usually have a combination of chemotherapy drugs. […] If your risk score is over 13, you might have a lower dose of chemotherapy to start with. This is to lower the risk of serious side effects. This is called induction chemotherapy.

• #30 Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2395266/

  A total of 59 women (23.6%) required second-line chemotherapy; 48 women had methotrexate resistance, eight had methotrexate toxicity and an empirical decision to change therapy was made in three. […] The overall survival of all patients was 98%, with 247 patients alive and well. […] In conclusion, methotrexate achieves high CR rates for low-risk persistent gestational trophoblastic disease. There are several different protocols for treatment administration, but larger comparative studies of their efficacy and toxicity, as well as long-term outcome are needed. However, the UK experience with low-dose intramuscular methotrexate is extensive and this is a relatively inexpensive and cost beneficial treatment.

• #31 Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6768657/

  Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. […] For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.

• #32

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  Chemoresistant GTN occurs when there is a plateau or an increase in hCG levels, with or without development of new metastases, often while the patient is receiving therapy. Relapsed GTN occurs when there are at least two elevated levels of hCG in the absence of pregnancy after achieving a period of normal hCG values with treatment. […] Most of these patients are salvageable by further chemotherapy; however, 20 % of patients will eventually become resistant to treatment and die. The overall 5-year survival was more than 90 % for patients with relapsed GTN, which was nearly 100 % for low-risk GTN and about 85 % for high-risk GTN. The prognosis for patients with chemoresistant GTN is worse than for those with relapsed GTN. […] For low-risk GTN patients who had been resistant to the single agent methotrexate, actinomycin-D is commonly used, followed by MAC (methotrexate, actinomycin-D, cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) if further salvage therapy is needed. […] For high-risk GTN patients who are resistant to first-line chemotherapy or have relapse, salvage combined chemotherapy with or without surgery will be required. Various salvage regimens are used worldwide; however, it is unclear which regimens are the most effective and the least toxic.

• #33 Gestational Trophoblastic Disease Treatment – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/patient/gtd-treatment-pdq

  Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. […] Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. […] Treatment of low-risk gestational trophoblastic neoplasia (GTN) (invasive mole or choriocarcinoma) may include chemotherapy with one or more anticancer drugs. […] Treatment of high-risk metastatic gestational trophoblastic neoplasia (invasive mole or choriocarcinoma) may include combination chemotherapy. […] Treatment of recurrent or resistant gestational trophoblastic tumor may include chemotherapy with one or more anticancer drugs for tumors previously treated with surgery.

• #34 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with GTN are subdivided into 2 groups: those with a WHO score of less than 7 (low-risk) and those with a score of 7 or higher and who are at high risk of therapy failure. Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy, as follows: Methotrexate is preferred by many US specialists, but actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. Six weeks of maintenance chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the serum hCG levels rise or plateau and the WHO score remains less than 7. […] Treatment in patients with WHO scores of 7 or higher is as follows: EMA-CO regimen A combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle, and cyclophosphamide and vincristine (Oncovin) administered in the second week. EMA-EP regimen Cisplatin and etoposide are substituted for cyclophosphamide and vincristine during the second week; sometimes reserved for patients in whom EMA-CO fails. At least 6 weeks of maintenance EMA-CO or EMA-EP are administered after a normal serum hCG level. Patients with liver metastasis are considered for liver irradiation (2000 cGy).

• #35 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  Patients with high-risk GTN have good prognosis if treated aggressively as follows: These patients are treated with a combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin) administered in the second week. This is known as the EMA-CO regimen. Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second week. This is known as the EMA-EP regimen. Some reserve the EMA-EP regimen for patients in whom EMA-CO fails. At least 6 weeks of maintenance of EMA-CO or EMA-EP are administered after a normal serum hCG level. […] Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with chemotherapy. Corticosteroids (dexamethasone) with systemic effect are administered to reduce brain edema. This is a common approach in the United States. Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross Hospital in the United Kingdom and has been reported by physicians from Duke University in North Carolina.

• #36 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.gestational-trophoblastic-disease-treatment-pdq%C2%AE-treatment-health-professional-information-nci.ncicdr0000062901

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration systematic review. […] The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG). […] A variety of regimens have been reported that include combinations of the following: Cisplatin, Etoposide, Bleomycin, Ifosfamide, Paclitaxel, Fluorouracil, Floxuridine.

• #37 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] The specifics are provided in Table 2 below. […] Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastases present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles. […] A variety of regimens have been used with no direct comparisons to determine whether one is superior. […] In part because of the inherent chemoresistance of PSTTs, resection of tumors is often considered in addition to chemotherapy regimens used for high-risk gestational trophoblastic neoplasias. […] A select group of patients with chemotherapy-resistant and clinically detectable gestational trophoblastic neoplasia may benefit from salvage surgery.

• #38 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.gestational-trophoblastic-disease-treatment-pdq%C2%AE-treatment-health-professional-information-nci.ncicdr0000062901

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration systematic review. […] The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG). […] A variety of regimens have been reported that include combinations of the following: Cisplatin, Etoposide, Bleomycin, Ifosfamide, Paclitaxel, Fluorouracil, Floxuridine.

• #39 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with GTN are subdivided into 2 groups: those with a WHO score of less than 7 (low-risk) and those with a score of 7 or higher and who are at high risk of therapy failure. Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy, as follows: Methotrexate is preferred by many US specialists, but actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. Six weeks of maintenance chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the serum hCG levels rise or plateau and the WHO score remains less than 7. […] Treatment in patients with WHO scores of 7 or higher is as follows: EMA-CO regimen A combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle, and cyclophosphamide and vincristine (Oncovin) administered in the second week. EMA-EP regimen Cisplatin and etoposide are substituted for cyclophosphamide and vincristine during the second week; sometimes reserved for patients in whom EMA-CO fails. At least 6 weeks of maintenance EMA-CO or EMA-EP are administered after a normal serum hCG level. Patients with liver metastasis are considered for liver irradiation (2000 cGy).

• #40 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI]

  https://awog.org/womens-health/health-library?DOCHWID=ncicdr0000062901

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastases present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles. […] A variety of regimens have been used with no direct comparisons to determine whether one is superior. Some of the regimens include the following: EMA/CO: Etoposide, methotrexate with leucovorin rescue, dactinomycin, cyclophosphamide, and vincristine. This appears to be the most commonly used regimen. […] In part because of the inherent chemoresistance of PSTTs, resection of tumors is often considered in addition to chemotherapy regimens used for high-risk gestational trophoblastic neoplasias.

• #41 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-EP regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid (15 mg every 12 hours), 12 doses (15 mg every 6 hours) are given starting 24 hours after the initiation of methotrexate infusion. Patients with liver metastasis are considered for liver irradiation (2000 cGy). […] Patients at high risk of early death (WHO score 12, large disease burden, major bleeding) are treated with low-dose induction etoposide/cisplatin (EP) consisting of 100 mg/m2 of etoposide and 20 mg/m2 of cisplatin on days 1 and 2, repeated weekly for 1-2 cycles before commencing EMA/CO. […] Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon. After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease.

• #42 Gestational Trophoblastic Disease Treatment – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/patient/gtd-treatment-pdq

  Gestational trophoblastic neoplasia (GTN) is a type of gestational trophoblastic disease (GTD) that is almost always malignant. […] A choriocarcinoma is a malignant tumor that forms from trophoblast cells and spreads to the muscle layer of the uterus and nearby blood vessels. […] The treatment of gestational trophoblastic neoplasia is based on the type of disease, stage, or risk group. […] Invasive moles and choriocarcinomas are treated based on risk groups. […] Treatment options also depend on whether the woman wishes to become pregnant in the future. […] There are different types of treatment for patients with gestational trophoblastic disease. […] Three types of standard treatment are used: Surgery, Chemotherapy, Radiation therapy. […] After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy after surgery to kill any cancer cells that are left.

• #43 Treatments for gestational trophoblastic disease | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/gestational-trophoblastic-disease/treatment

  Chemotherapy is usually given to treat invasive moles and gestational choriocarcinoma. In some cases, it may be used to treat placental site trophoblastic tumours (PSTTs) and epithelioid trophoblastic tumours (ETTs). […] Radiation therapy uses high-energy rays or particles to destroy cancer cells. Some people with cancerous GTD may be offered radiation therapy.

• #44 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  Patients with high-risk GTN have good prognosis if treated aggressively as follows: These patients are treated with a combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin) administered in the second week. This is known as the EMA-CO regimen. Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second week. This is known as the EMA-EP regimen. Some reserve the EMA-EP regimen for patients in whom EMA-CO fails. At least 6 weeks of maintenance of EMA-CO or EMA-EP are administered after a normal serum hCG level. […] Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with chemotherapy. Corticosteroids (dexamethasone) with systemic effect are administered to reduce brain edema. This is a common approach in the United States. Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross Hospital in the United Kingdom and has been reported by physicians from Duke University in North Carolina.

• #45 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Whole brain irradiation (3000 cGy) is given in combination with chemotherapy; dexamethasone is administered to reduce brain edema (most common approach in US). Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity, followed by moderate- and high-dose intravenous methotrexate and, at some centers, intrathecal methotrexate (approach used in selected institutions). A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at IV doses of 600 mg/m. In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-EP regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid (15 mg every 12 hours), 12 doses (15 mg every 6 hours) are given, starting 24 hours after the initiation of methotrexate infusion.

• #46 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-EP regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid (15 mg every 12 hours), 12 doses (15 mg every 6 hours) are given starting 24 hours after the initiation of methotrexate infusion. Patients with liver metastasis are considered for liver irradiation (2000 cGy). […] Patients at high risk of early death (WHO score 12, large disease burden, major bleeding) are treated with low-dose induction etoposide/cisplatin (EP) consisting of 100 mg/m2 of etoposide and 20 mg/m2 of cisplatin on days 1 and 2, repeated weekly for 1-2 cycles before commencing EMA/CO. […] Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon. After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease.

• #47 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Whole brain irradiation (3000 cGy) is given in combination with chemotherapy; dexamethasone is administered to reduce brain edema (most common approach in US). Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity, followed by moderate- and high-dose intravenous methotrexate and, at some centers, intrathecal methotrexate (approach used in selected institutions). A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at IV doses of 600 mg/m. In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-EP regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid (15 mg every 12 hours), 12 doses (15 mg every 6 hours) are given, starting 24 hours after the initiation of methotrexate infusion.

• #48

• #49 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon. After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease. […] Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage; hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Craniotomy may be needed to control bleeding and provide decompression. Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission. A complete response (normalization of serum hCG) occurs in 30-40% of patients with newly diagnosed low-risk non-metastatic GTN who undergo a repeat DC. Hysterectomy, or a repeat DC in patients with persistent tissue on pelvic ultrasonography, may reduce the number of chemotherapy cycles needed to achieve remission. A hysterectomy is the treatment of choice for PSTT; the ovaries do not need to be removed if the patient is premenopausal.

• #50 Treatments for gestational trophoblastic disease | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/gestational-trophoblastic-disease/treatment

  Surgery is the main treatment for non-cancerous types of gestational trophoblastic disease (GTD). A combination of treatments may be used for cancerous GTD (also called gestational trophoblastic neoplasia, or GTN). These treatments can include surgery, chemotherapy and radiation therapy. […] Surgery is usually used to treat non-cancerous GTD. It is also used to treat some types of cancerous GTD. […] A hysterectomy is done to completely remove cancer that is in the uterus or to reduce the chance that cancer will develop. A hysterectomy is often used to treat placental site trophoblastic tumours (PSTTs) and epithelioid trophoblastic tumours (ETTs) because they don’t usually respond well to chemotherapy. […] Chemotherapy uses drugs to destroy cancer cells. It can be used to treat some types of cancerous GTD.

• #51 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon. After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease. […] Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage; hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Craniotomy may be needed to control bleeding and provide decompression. Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission. A complete response (normalization of serum hCG) occurs in 30-40% of patients with newly diagnosed low-risk non-metastatic GTN who undergo a repeat DC. Hysterectomy, or a repeat DC in patients with persistent tissue on pelvic ultrasonography, may reduce the number of chemotherapy cycles needed to achieve remission. A hysterectomy is the treatment of choice for PSTT; the ovaries do not need to be removed if the patient is premenopausal.

• #52 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI]

  https://awog.org/womens-health/health-library?DOCHWID=ncicdr0000062901

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastases present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles. […] A variety of regimens have been used with no direct comparisons to determine whether one is superior. Some of the regimens include the following: EMA/CO: Etoposide, methotrexate with leucovorin rescue, dactinomycin, cyclophosphamide, and vincristine. This appears to be the most commonly used regimen. […] In part because of the inherent chemoresistance of PSTTs, resection of tumors is often considered in addition to chemotherapy regimens used for high-risk gestational trophoblastic neoplasias.

• #53 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  A gynecologic oncologist experienced in managing GTN should be consulted. Patients with resistant disease may benefit from consultation at a regional trophoblastic disease center. […] A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the total number of chemotherapy cycles needed to achieve remission. Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. A repeat DC in the presence of persistent tissue on pelvic ultrasonography may reduce the number of chemotherapy cycles needed to achieve remission. Craniotomy may be needed to control bleeding and provide decompression. Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission.

• #54

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  Gestational trophoblastic neoplasia (GTN) is highly chemosensitive and has a high cure rate. Since the introduction of chemotherapy, reliable measurement of human chorionic gonadotropin (hCG) levels, and individualized risk-based therapy into the management of GTN, almost all low-risk and more than 80 % of high-risk GTN cases are curable. However, approximately 25 % of high-risk GTN developed resistance to chemotherapy or relapsed after completion of initial therapy, which often necessitate salvage combination chemotherapy. […] Recently, measurement of hyperglycosylated hCG has been proposed for the management of patients with quiescent GTD. Although representing a small proportion of GTD cases, the management of patients with chemoresistant and quiescent GTD often poses challenges to medical practitioners.

• #55

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  Chemoresistant GTN occurs when there is a plateau or an increase in hCG levels, with or without development of new metastases, often while the patient is receiving therapy. Relapsed GTN occurs when there are at least two elevated levels of hCG in the absence of pregnancy after achieving a period of normal hCG values with treatment. […] Most of these patients are salvageable by further chemotherapy; however, 20 % of patients will eventually become resistant to treatment and die. The overall 5-year survival was more than 90 % for patients with relapsed GTN, which was nearly 100 % for low-risk GTN and about 85 % for high-risk GTN. The prognosis for patients with chemoresistant GTN is worse than for those with relapsed GTN. […] For low-risk GTN patients who had been resistant to the single agent methotrexate, actinomycin-D is commonly used, followed by MAC (methotrexate, actinomycin-D, cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) if further salvage therapy is needed. […] For high-risk GTN patients who are resistant to first-line chemotherapy or have relapse, salvage combined chemotherapy with or without surgery will be required. Various salvage regimens are used worldwide; however, it is unclear which regimens are the most effective and the least toxic.

• #56 Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6768657/

  For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. […] Salvage chemotherapy in high-risk GTN is a much more difficult clinical scenario than salvage chemotherapy in low-risk GTN. Risk factors for resistance to treatment in high-risk GTN include the number and sites of metastases (brain, liver and gastrointestinal metastases have a worse prognosis), incomplete previous treatments, and the age of the tumour.

• #57 Gestational Trophoblastic Disease – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/gynecologic-tumors/gestational-trophoblastic-disease

  All patients with high-risk gestational trophoblastic neoplasia (WHO risk score 6) should be referred to specialists. […] Programmed death receptor 1 (PD-1) is present in almost all gestational trophoblastic disease lesions. Some patients with drug-resistant gestational trophoblastic neoplasia have been treated with checkpoint inhibitors (pembrolizumab, avelumab) with some benefit. […] Cure rates are […] Low-risk: 90 to 95% […] High-risk: 60 to 80% […] Treatment of high-risk gestational trophoblastic neoplasia resistant to initial chemotherapy is difficult. Options include […] EMA/EP (etoposide/methotrexate/actinomycin D/etoposide/cisplatin) […] Multi-day etoposide/cisplatin regimens […] High-dose chemotherapy with stem cell support. […] If treatment is successful, hCG levels should decrease by 10% over three cycles of treatment. […] An alternative treatment is needed if there is significant toxicity or if hCG levels […] Do not decrease as expected. […] Increase 10% over two cycles.

• #58 Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6768657/

  For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. […] Salvage chemotherapy in high-risk GTN is a much more difficult clinical scenario than salvage chemotherapy in low-risk GTN. Risk factors for resistance to treatment in high-risk GTN include the number and sites of metastases (brain, liver and gastrointestinal metastases have a worse prognosis), incomplete previous treatments, and the age of the tumour.

• #59 Gestational Trophoblastic Disease Treatment (PDQ®): Treatment – Health Professional Information [NCI] | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.gestational-trophoblastic-disease-treatment-pdq%C2%AE-treatment-health-professional-information-nci.ncicdr0000062901

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. Chemotherapy is determined by the patient’s modified World Health Organization score. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] The use of chemotherapy in the first-line management of low-risk GTN has been assessed in a Cochrane Collaboration systematic review. […] The initial regimen is generally given until a normal beta human chorionic gonadotropin (beta-hCG) (for the institution) is achieved and sustained for 3 consecutive weeks (or at least for one treatment cycle beyond normalization of the beta-hCG). […] A variety of regimens have been reported that include combinations of the following: Cisplatin, Etoposide, Bleomycin, Ifosfamide, Paclitaxel, Fluorouracil, Floxuridine.

• #60 Cancer drug treatment for invasive mole and choriocarcinoma | Gestational trophoblastic disease (GTD) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/gestational-trophoblastic-disease-gtd/invasive-mole-choriocarcinoma/treatment/cancer-drug-treatment

  Some women might develop resistance to chemotherapy drugs. These women might have treatment with an immunotherapy drug called pembrolizumab (Keytruda). […] You will be closely monitored with blood and urine tests during and after your treatment. […] Survival for invasive mole and choriocarcinoma is very high. Nearly all women are cured.

• #61 SciELO Brazil – Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia – systematic review with a presentation of the first 4 Brazilian cases Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplas

  https://www.scielo.br/j/clin/a/qGcjVrQrKKMvQMTw87HnThd/

  ObjectiveTo evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. […] Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment. […] Pembrolizumab (which targets PD-1 on T-cells) was the first immunotherapy used for multi-drug resistant GTN, with a 75% (3/4 patients) Complete Response (CR). […] These results led the National Comprehensive Cancer Network to recommend immunotherapy as a therapeutic option for cases of chemoresistant GTN.

• #62 SciELO Brazil – Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia – systematic review with a presentation of the first 4 Brazilian cases Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplas

  https://www.scielo.br/j/clin/a/qGcjVrQrKKMvQMTw87HnThd/

  ObjectiveTo evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. […] Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment. […] Pembrolizumab (which targets PD-1 on T-cells) was the first immunotherapy used for multi-drug resistant GTN, with a 75% (3/4 patients) Complete Response (CR). […] These results led the National Comprehensive Cancer Network to recommend immunotherapy as a therapeutic option for cases of chemoresistant GTN.

• #63 SciELO Brazil – Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia – systematic review with a presentation of the first 4 Brazilian cases Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplas

  https://www.scielo.br/j/clin/a/qGcjVrQrKKMvQMTw87HnThd/

  Patients with MTX chemoresistance who were willing and able to be treated with avelumab (anti-PD-L1 human monoclonal antibody, 10 mg/kg intravenously every 2 weeks) received this treatment. On the other hand, patients with GTN with chemoresistance to at least 2 sequential multiagent regimens were treated with pembrolizumab (anti-PD-1 human monoclonal antibody, initially 3 mg/kg or more recently 200 mg fixed dose, intravenously every 3 weeks) if they wished and this drug was available. […] The primary outcome of this study was the occurrence of complete remission attested by 3 weekly hCG levels 5 IU/L. […] The systematic review showed that pembrolizumab is effective for the treatment of GTN regardless of its histological subtype, achieving a good response in cases of CC, PSTT, or ETT. […] Pembrolizumab induced remission in 86.7% (13/15) of GTN chemoresistant to multiagent regimens.

• #64 SciELO Brazil – Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia – systematic review with a presentation of the first 4 Brazilian cases Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplas

  https://www.scielo.br/j/clin/a/qGcjVrQrKKMvQMTw87HnThd/

  ObjectiveTo evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. […] Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment. […] Pembrolizumab (which targets PD-1 on T-cells) was the first immunotherapy used for multi-drug resistant GTN, with a 75% (3/4 patients) Complete Response (CR). […] These results led the National Comprehensive Cancer Network to recommend immunotherapy as a therapeutic option for cases of chemoresistant GTN.

• #65 SciELO Brazil – Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplasia – systematic review with a presentation of the first 4 Brazilian cases Immunotherapy in the treatment of chemoresistant gestational trophoblastic neoplas

  https://www.scielo.br/j/clin/a/qGcjVrQrKKMvQMTw87HnThd/

  Patients with MTX chemoresistance who were willing and able to be treated with avelumab (anti-PD-L1 human monoclonal antibody, 10 mg/kg intravenously every 2 weeks) received this treatment. On the other hand, patients with GTN with chemoresistance to at least 2 sequential multiagent regimens were treated with pembrolizumab (anti-PD-1 human monoclonal antibody, initially 3 mg/kg or more recently 200 mg fixed dose, intravenously every 3 weeks) if they wished and this drug was available. […] The primary outcome of this study was the occurrence of complete remission attested by 3 weekly hCG levels 5 IU/L. […] The systematic review showed that pembrolizumab is effective for the treatment of GTN regardless of its histological subtype, achieving a good response in cases of CC, PSTT, or ETT. […] Pembrolizumab induced remission in 86.7% (13/15) of GTN chemoresistant to multiagent regimens.

• #66 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy is the main treatment for GTN and is generally highly effective. […] Patients can preserve fertility and still be cured with chemotherapy even in the presence of widespread disease. […] Surgery may also be used to remove cancer involving the lungs and other organs that has not gone away with drug therapy. […] Placental-site and epithelioid trophoblastic tumors are less sensitive than choriocarcinoma to chemotherapy. […] Most women who require treatment for GTN can become pregnant again and have normal pregnancies. After chemotherapy is completed, women should postpone pregnancy for 12 months (24 months for women with stage IV disease) while they are being followed with hormone testing to make sure the tumor does not recur.

• #67

  http://www.bccancer.bc.ca/health-professionals/clinical-resources/cancer-management-manual/gynecology/gestational-trophoblastic-neoplasia

  Patients with stage IV and stage II-III GTN with a WHO score of 7 are considered to have a high-risk GTN. […] If GTN is resistance to treatment (new metastasis or increase/plateau in 2 consecutive values over a 2 week period) or has relapsed, an alternative treatment is considered. […] Since PSTT and ETT are relatively chemo-resistant, hysterectomy should be considered in the management of these tumours.

• #68 Gestational Trophoblastic Disease | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/22233

  High-risk (a cumulative score 7; see staging section below) and stage II to IV disease are treated with multi-agent chemotherapy, adjuvant radiation, and surgery. […] Standard Gestational Trophoblastic Disease Treatments include DE, chemotherapy, hysterectomy, or a combination of these modalities. […] Initial management of nonmetastatic PSTT or ETT is hysterectomy and salpingectomy, with or without lymph node sampling. […] In metastatic PSTT or ETT cases, if feasible, hysterectomy, salpingectomy, and resection of metastatic disease are followed by platinum-based chemotherapy. […] Prophylactic chemotherapy has been proposed in place of monitoring hCG levels until disease clearance criteria are met. […] Pembrolizumab is one of the drugs studied for use in this situation, and the results show that it represents a valuable new approach for treating drug-resistant GTN.

• #69 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Chemotherapy is ultimately required for persistence or neoplastic transformation in about 15% to 20% of patients after evacuation of a complete HM but for fewer than 5% of patients with partial HM. […] Multiagent chemotherapy is standard for the initial management of high-risk gestational trophoblastic neoplasia (GTN). […] The specifics are provided in Table 2 below. […] Cycles are repeated every 2 weeks (on days 15, 16, and 22) until any metastases present at diagnosis disappear and serum beta-human chorionic gonadotropin (beta-hCG) has normalized, then the treatment is usually continued for an additional three to four cycles. […] A variety of regimens have been used with no direct comparisons to determine whether one is superior. […] In part because of the inherent chemoresistance of PSTTs, resection of tumors is often considered in addition to chemotherapy regimens used for high-risk gestational trophoblastic neoplasias. […] A select group of patients with chemotherapy-resistant and clinically detectable gestational trophoblastic neoplasia may benefit from salvage surgery.

• #70 Treatments for gestational trophoblastic disease | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/gestational-trophoblastic-disease/treatment

  Surgery is the main treatment for non-cancerous types of gestational trophoblastic disease (GTD). A combination of treatments may be used for cancerous GTD (also called gestational trophoblastic neoplasia, or GTN). These treatments can include surgery, chemotherapy and radiation therapy. […] Surgery is usually used to treat non-cancerous GTD. It is also used to treat some types of cancerous GTD. […] A hysterectomy is done to completely remove cancer that is in the uterus or to reduce the chance that cancer will develop. A hysterectomy is often used to treat placental site trophoblastic tumours (PSTTs) and epithelioid trophoblastic tumours (ETTs) because they don’t usually respond well to chemotherapy. […] Chemotherapy uses drugs to destroy cancer cells. It can be used to treat some types of cancerous GTD.

• #71

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  Although GTN is chemosensitive, surgery may be required and can result in a cure in selected patients with chemoresistant or persistent foci of disease in the uterus or metastatic sites. […] Factors that have been found to influence the therapeutic response to surgical interventions included age, type of antecedent pregnancy, preoperative hCG level, time from diagnosis to surgery, number of preoperative disease sites, preoperative WHO risk score, and histologic type. […] Quiescent, or inactive, GTD occurs in a proportion of patients where there is a persistently low level of hCG in the absence of any clinical or radiological evidence of GTN. […] These syncytiotrophoblast cells do not respond to chemotherapy, and surgery does not result in normalization of hCG. […] Hypergylcosylated hCG (hCG-H) measurement has been proposed for the management of patients with quiescent GTD. […] In this condition, chemotherapy was ineffective because the tissue in quiescent GTD is not growing, and in most cases hCG returned to normal within 6 months. Thus, it was suggested that when hCG-H is undetectable, even with persistently low hCG levels, intervention is not needed. Meanwhile, if hCG-H becomes detectable, then this may indicate clinically relevant disease and therapy may be required.

• #72

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  Although GTN is chemosensitive, surgery may be required and can result in a cure in selected patients with chemoresistant or persistent foci of disease in the uterus or metastatic sites. […] Factors that have been found to influence the therapeutic response to surgical interventions included age, type of antecedent pregnancy, preoperative hCG level, time from diagnosis to surgery, number of preoperative disease sites, preoperative WHO risk score, and histologic type. […] Quiescent, or inactive, GTD occurs in a proportion of patients where there is a persistently low level of hCG in the absence of any clinical or radiological evidence of GTN. […] These syncytiotrophoblast cells do not respond to chemotherapy, and surgery does not result in normalization of hCG. […] Hypergylcosylated hCG (hCG-H) measurement has been proposed for the management of patients with quiescent GTD. […] In this condition, chemotherapy was ineffective because the tissue in quiescent GTD is not growing, and in most cases hCG returned to normal within 6 months. Thus, it was suggested that when hCG-H is undetectable, even with persistently low hCG levels, intervention is not needed. Meanwhile, if hCG-H becomes detectable, then this may indicate clinically relevant disease and therapy may be required.

• #73

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  The International Society for the Study of Trophoblastic Disease 2001 recommended that in the management of patients with quiescent GTD, false-positive hCG results should be ruled out and that investigations for evidence of disease should be performed. Immediate chemotherapy or surgery should be avoided, and long-term monitoring with serial hCG while avoiding pregnancy should be advised. […] Utilization of hCG-H could improve the management of quiescent GTD and help to identify the characteristics of the condition before starting treatment.

• #74

  https://link.springer.com/article/10.1007/s13669-013-0071-6

  The International Society for the Study of Trophoblastic Disease 2001 recommended that in the management of patients with quiescent GTD, false-positive hCG results should be ruled out and that investigations for evidence of disease should be performed. Immediate chemotherapy or surgery should be avoided, and long-term monitoring with serial hCG while avoiding pregnancy should be advised. […] Utilization of hCG-H could improve the management of quiescent GTD and help to identify the characteristics of the condition before starting treatment.

• #75 Gestational Trophoblastic Disease Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq

  Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. […] Chemotherapy is necessary when there is the following: A rising beta-hCG titer for 2 weeks (3 titers), A tissue diagnosis of choriocarcinoma, A plateau of the beta-hCG for 3 weeks, Persistence of detectable beta-hCG 6 months after mole evacuation, Metastatic disease, An elevation in beta-hCG after a normal value, Postevacuation hemorrhage not caused by retained tissues.

• #76 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy for GTN continues until hCG normalizes. Once this is achieved, three additional cycles of consolidation chemotherapy are given. […] GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and rarely need treatment, while women with GTN also have a very good prognosis but require treatment. Choriocarcinoma, for example, is an uncommon yet almost always curable cancer. […] About 85 to 90 percent of women with low-risk GTN are cured by the initial chemotherapy, and the remaining are cured by stronger combinations of drugs, or by surgery. […] Similarly, 85-90 percent of women who develop high-risk GTN are cured by chemotherapy used together with selective surgery and radiation. […] Three kinds of treatment can be used for GTN: Chemotherapy (using drugs to eliminate the cancer), Radiation therapy (uses high energy x-rays to eliminate cancer cells and shrink tumors), Surgery (removing the cancer).

• #77 Information about choriocarcinoma | Imperial College Healthcare NHS Trust

  https://www.imperial.nhs.uk/our-services/cancer-services/gestational-trophoblastic-disease/information-about-choriocarcinoma

  Find out more about choriocarcinoma and how we diagnose and treat it at Charing Cross Hospital. […] You will initially be treated for choriocarcinoma as an inpatient at Charing Cross Hospital, generally with EMA-CO chemotherapy. […] Fortunately choriocarcinoma is highly sensitive to chemotherapy, with a very high expectation of cure once diagnosed. […] Treatment for choriocarcinoma usually takes four months to complete and the cure rate is over 95 per cent. The treatment is continued for six to eight weeks after the hCG level has returned to normal.

• #78 Gestational Trophoblastic Neoplasia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/279116-overview

  Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon. After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease. […] Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage; hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Craniotomy may be needed to control bleeding and provide decompression. Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission. A complete response (normalization of serum hCG) occurs in 30-40% of patients with newly diagnosed low-risk non-metastatic GTN who undergo a repeat DC. Hysterectomy, or a repeat DC in patients with persistent tissue on pelvic ultrasonography, may reduce the number of chemotherapy cycles needed to achieve remission. A hysterectomy is the treatment of choice for PSTT; the ovaries do not need to be removed if the patient is premenopausal.

• #79 Gestational Trophoblastic Disease – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/gynecologic-tumors/gestational-trophoblastic-disease

  All patients with high-risk gestational trophoblastic neoplasia (WHO risk score 6) should be referred to specialists. […] Programmed death receptor 1 (PD-1) is present in almost all gestational trophoblastic disease lesions. Some patients with drug-resistant gestational trophoblastic neoplasia have been treated with checkpoint inhibitors (pembrolizumab, avelumab) with some benefit. […] Cure rates are […] Low-risk: 90 to 95% […] High-risk: 60 to 80% […] Treatment of high-risk gestational trophoblastic neoplasia resistant to initial chemotherapy is difficult. Options include […] EMA/EP (etoposide/methotrexate/actinomycin D/etoposide/cisplatin) […] Multi-day etoposide/cisplatin regimens […] High-dose chemotherapy with stem cell support. […] If treatment is successful, hCG levels should decrease by 10% over three cycles of treatment. […] An alternative treatment is needed if there is significant toxicity or if hCG levels […] Do not decrease as expected. […] Increase 10% over two cycles.

• #80 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy is the main treatment for GTN and is generally highly effective. […] Patients can preserve fertility and still be cured with chemotherapy even in the presence of widespread disease. […] Surgery may also be used to remove cancer involving the lungs and other organs that has not gone away with drug therapy. […] Placental-site and epithelioid trophoblastic tumors are less sensitive than choriocarcinoma to chemotherapy. […] Most women who require treatment for GTN can become pregnant again and have normal pregnancies. After chemotherapy is completed, women should postpone pregnancy for 12 months (24 months for women with stage IV disease) while they are being followed with hormone testing to make sure the tumor does not recur.

• #81 Gestational trophoblastic disease – Wikipedia

  https://en.wikipedia.org/wiki/Gestational_trophoblastic_disease

  Treatment is always necessary. […] The treatment for hydatidiform mole consists of the evacuation of pregnancy. Evacuation will lead to the relief of symptoms, and also prevent later complications. Suction curettage is the preferred method of evacuation. Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated with systemic (intravenous) methotrexate. […] The treatment for invasive mole or choriocarcinoma generally is the same. Both are usually treated with chemotherapy. Methotrexate and dactinomycin are among the chemotherapy drugs used in GTD. […] Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. […] Follow up is necessary in all women with gestational trophoblastic disease, because of the possibility of persistent disease, or because of the risk of developing malignant uterine invasion or malignant metastatic disease even after treatment in some women with certain risk factors.

• #82 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy is the main treatment for GTN and is generally highly effective. […] Patients can preserve fertility and still be cured with chemotherapy even in the presence of widespread disease. […] Surgery may also be used to remove cancer involving the lungs and other organs that has not gone away with drug therapy. […] Placental-site and epithelioid trophoblastic tumors are less sensitive than choriocarcinoma to chemotherapy. […] Most women who require treatment for GTN can become pregnant again and have normal pregnancies. After chemotherapy is completed, women should postpone pregnancy for 12 months (24 months for women with stage IV disease) while they are being followed with hormone testing to make sure the tumor does not recur.

• #83 Gestational Trophoblastic Disease (GTD) | Foundation For Women’s Cancer

  https://foundationforwomenscancer.org/gynecologic-cancers/gestational-trophoblastic-disease-gtd/

  GTD Treatment and Side Effects […] After the diagnosis of complete or partial hydatidiform mole is made or suspected, the uterine contents are removed by dilation and evacuation (DE). Hysterectomy may be advisable in older patients who have completed childbearing to reduce the risk of malignancy. After the uterus is emptied, testing for human chorionic gonadotropin should be performed every week in order to determine if the molar pregnancy is malignant. If the molar pregnancy is benign the hormone level will become undetectable in 8-12 weeks. Hormone testing should be continued until three weekly negative levels are obtained, then followed by monthly tests for six months, after which pregnancy is permitted. During the six month follow-up it is important to avoid pregnancy. The use of oral contraceptives is safe.

• #84 GTD Overview

  https://gynonc.nm.org/gtd-overview.html

  When GTN is diagnosed, evaluation and staging (including blood work, laboratory tests, X-rays, MRI and/or CT scans) is the next step to determine risk factors and treatment. Treatment is then based on classification into risk groups defined by a combination of stage (where the disease is located) and score (prognostic factors). Use of this staging system is essential for determining the most appropriate initial therapy to assure the best possible outcomes with the least toxicity. […] Women with nonmetastatic (stage I) and low-risk metastatic (stages II III, score 7) GTN can be treated with low-toxicity, single-agent chemotherapy with resulting survival rates approaching 100 percent. At the Brewer Center, the overall survival rate for low-risk GTN is 100 percent. […] Women classified as having high-risk metastatic disease (stages II-III, score 7 and stage IV) need to be treated in a more aggressive manner with multi-agent chemotherapy +/- adjuvant radiation or surgery to achieve cure rates of 80 to 90 percent. At our Center, overall survival rates for high-risk GTN are up to 93 percent. […] Successful treatment of GTN with chemotherapy has resulted in a large number of women who maintain their reproductive function. Most women resume normal ovarian function, exhibit no increase in infertility, and can anticipate successful pregnancy if desired.

• #85 Persistent trophoblastic disease and choriocarcinoma | nidirect

  https://www.nidirect.gov.uk/conditions/persistent-trophoblastic-disease-and-choriocarcinoma

  Persistent trophoblastic disease and choriocarcinoma are very rare pregnancy-related tumours. They are known as gestational trophoblastic tumours (GTTs). […] Chemotherapy is usually used to treat the condition. Treatment is successful in curing almost all cases of persistent trophoblastic disease. […] Chemotherapy is used to treat choriocarcinoma and usually successfully cures it. […] Overall, the outlook for persistent trophoblastic disease and choriocarcinoma is excellent. 98 to 100 per cent of women who develop a gestational trophoblastic cancer are cured.

• #86 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy for GTN continues until hCG normalizes. Once this is achieved, three additional cycles of consolidation chemotherapy are given. […] GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and rarely need treatment, while women with GTN also have a very good prognosis but require treatment. Choriocarcinoma, for example, is an uncommon yet almost always curable cancer. […] About 85 to 90 percent of women with low-risk GTN are cured by the initial chemotherapy, and the remaining are cured by stronger combinations of drugs, or by surgery. […] Similarly, 85-90 percent of women who develop high-risk GTN are cured by chemotherapy used together with selective surgery and radiation. […] Three kinds of treatment can be used for GTN: Chemotherapy (using drugs to eliminate the cancer), Radiation therapy (uses high energy x-rays to eliminate cancer cells and shrink tumors), Surgery (removing the cancer).

• #87 Cancer drug treatment for invasive mole and choriocarcinoma | Gestational trophoblastic disease (GTD) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/gestational-trophoblastic-disease-gtd/invasive-mole-choriocarcinoma/treatment/cancer-drug-treatment

  Some women might develop resistance to chemotherapy drugs. These women might have treatment with an immunotherapy drug called pembrolizumab (Keytruda). […] You will be closely monitored with blood and urine tests during and after your treatment. […] Survival for invasive mole and choriocarcinoma is very high. Nearly all women are cured.

• #88 Gestational Trophoblastic Disease (GTD) | Foundation For Women’s Cancer

  https://foundationforwomenscancer.org/gynecologic-cancers/gestational-trophoblastic-disease-gtd/

  Recurrent Disease […] GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and women with malignant GTD (called GTN) usually have a very good prognosis. Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumor and life-threatening disease, it is very sensitive to chemotherapy. 85 to 90 percent of women with low-risk malignant GTD are cured by the initial chemotherapy and the remaining are cured by the use of stronger combinations of drugs or surgery. Similarly, 85 to 90 percent of women who develop high-risk malignant GTD are cured by chemotherapy used together with the selective use of surgery and radiation. Approximately ten to 15 percent of women with high-risk malignant GTD will develop drug resistance after prolonged chemotherapy. This group is made up of patients with stage IV disease that involves distant organs such as the brain, liver and bowel. Specially designed chemotherapy treatments using drugs that have been shown to be effective against other cancers are being employed to prolong life for many of these women.

• #89 Choriocarcinoma – UF Health

  https://ufhealth.org/conditions-and-treatments/choriocarcinoma

  Choriocarcinoma is a fast-growing cancer that occurs in a woman’s uterus (womb). […] Choriocarcinoma is a type of gestational trophoblastic disease. […] After you are diagnosed, a careful history and exam will be done to make sure the cancer has not spread to other organs. Chemotherapy is the main type of treatment. It is usually effective. […] Hysterectomy to remove the womb and radiation treatment are rarely needed. […] Most women whose cancer has not spread can be cured and will still be able to have children. A choriocarcinoma may come back within a few months to 3 years after treatment. […] The condition is harder to cure if the cancer has spread and one or more of the following happens: Disease spreads to the liver or brain, Pregnancy hormone (HCG) level is higher than 40,000 mIU/mL when treatment begins, Cancer returns after having chemotherapy, Symptoms or pregnancy occurred for more than 4 months before treatment began, Choriocarcinoma occurred after a pregnancy that resulted in the birth of a child. […] Many women (about 70%) who have a poor outlook at first go into remission (a disease-free state).

• #90 Choriocarcinoma – UF Health

  https://ufhealth.org/conditions-and-treatments/choriocarcinoma

  Choriocarcinoma is a fast-growing cancer that occurs in a woman’s uterus (womb). […] Choriocarcinoma is a type of gestational trophoblastic disease. […] After you are diagnosed, a careful history and exam will be done to make sure the cancer has not spread to other organs. Chemotherapy is the main type of treatment. It is usually effective. […] Hysterectomy to remove the womb and radiation treatment are rarely needed. […] Most women whose cancer has not spread can be cured and will still be able to have children. A choriocarcinoma may come back within a few months to 3 years after treatment. […] The condition is harder to cure if the cancer has spread and one or more of the following happens: Disease spreads to the liver or brain, Pregnancy hormone (HCG) level is higher than 40,000 mIU/mL when treatment begins, Cancer returns after having chemotherapy, Symptoms or pregnancy occurred for more than 4 months before treatment began, Choriocarcinoma occurred after a pregnancy that resulted in the birth of a child. […] Many women (about 70%) who have a poor outlook at first go into remission (a disease-free state).

• #91 Choriocarcinoma – UF Health

  https://ufhealth.org/conditions-and-treatments/choriocarcinoma

  Choriocarcinoma is a fast-growing cancer that occurs in a woman’s uterus (womb). […] Choriocarcinoma is a type of gestational trophoblastic disease. […] After you are diagnosed, a careful history and exam will be done to make sure the cancer has not spread to other organs. Chemotherapy is the main type of treatment. It is usually effective. […] Hysterectomy to remove the womb and radiation treatment are rarely needed. […] Most women whose cancer has not spread can be cured and will still be able to have children. A choriocarcinoma may come back within a few months to 3 years after treatment. […] The condition is harder to cure if the cancer has spread and one or more of the following happens: Disease spreads to the liver or brain, Pregnancy hormone (HCG) level is higher than 40,000 mIU/mL when treatment begins, Cancer returns after having chemotherapy, Symptoms or pregnancy occurred for more than 4 months before treatment began, Choriocarcinoma occurred after a pregnancy that resulted in the birth of a child. […] Many women (about 70%) who have a poor outlook at first go into remission (a disease-free state).

• #92 Choriocarcinoma: Causes, Symptoms, Treatment & Prevention

  https://my.clevelandclinic.org/health/diseases/24863-choriocarcinoma

  Choriocarcinoma is most common in people who have a molar pregnancy (when the sperm and egg join incorrectly and make a hydatidiform mole). […] Most cases of choriocarcinoma are cured by chemotherapy treatment. […] The main treatment for choriocarcinoma is chemotherapy. Chemotherapy is a drug that kills cancer cells. Some people may also need surgery to remove their uterus (hysterectomy), radiation or a combination of treatments. […] Yes, choriocarcinoma is curable. Treatment with chemotherapy is usually successful in curing it. The prognosis is better when choriocarcinoma is caught early, before it spreads to other parts of your body. […] Non-gestational choriocarcinoma (not related to a prior abnormal pregnancy/placental tissue) has a worse prognosis and is less chemosensitive, which means chemotherapy may not be as effective in killing the cancer cells.

• #93 Advances in the diagnosis and early management of gestational trophoblastic disease | BMJ Medicine

  https://bmjmedicine.bmj.com/content/1/1/e000321

  Gestational trophoblastic disease (GTD) describes a heterogeneous group of disorders that arise from abnormal proliferation of placental trophoblastic tissue. […] GTN is the most curable of all gynaecological malignancies with cure rates approaching 100%, even in the presence of metastatic disease. […] This review focuses on the diagnosis and early management of GTD over the past decade and we direct the reader to other publications for expert opinion on the chemotherapeutic management of GTN. […] The diagnosis of GTN is largely based on a combination of obstetric history and elevated concentrations of hCG. […] After molar pregnancy, plateaued or rising hCG concentrations are indicative of GTN. […] Most women with molar pregnancy do not require further treatment following uterine evacuation of the products of conception. However, some women develop disease persistence and progress to malignant disease requiring chemotherapy or further surgical intervention.

• #94 Gestational Trophoblastic Disease (GTD) Treatment | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/gestational-trophoblastic-disease/treatment

  Chemotherapy for GTN continues until hCG normalizes. Once this is achieved, three additional cycles of consolidation chemotherapy are given. […] GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and rarely need treatment, while women with GTN also have a very good prognosis but require treatment. Choriocarcinoma, for example, is an uncommon yet almost always curable cancer. […] About 85 to 90 percent of women with low-risk GTN are cured by the initial chemotherapy, and the remaining are cured by stronger combinations of drugs, or by surgery. […] Similarly, 85-90 percent of women who develop high-risk GTN are cured by chemotherapy used together with selective surgery and radiation. […] Three kinds of treatment can be used for GTN: Chemotherapy (using drugs to eliminate the cancer), Radiation therapy (uses high energy x-rays to eliminate cancer cells and shrink tumors), Surgery (removing the cancer).

• #95 Gestational Trophoblastic Disease (GTD) | Foundation For Women’s Cancer

  https://foundationforwomenscancer.org/gynecologic-cancers/gestational-trophoblastic-disease-gtd/

  Recurrent Disease […] GTD is a highly curable disease. Women with hydatidiform mole have an excellent prognosis and women with malignant GTD (called GTN) usually have a very good prognosis. Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumor and life-threatening disease, it is very sensitive to chemotherapy. 85 to 90 percent of women with low-risk malignant GTD are cured by the initial chemotherapy and the remaining are cured by the use of stronger combinations of drugs or surgery. Similarly, 85 to 90 percent of women who develop high-risk malignant GTD are cured by chemotherapy used together with the selective use of surgery and radiation. Approximately ten to 15 percent of women with high-risk malignant GTD will develop drug resistance after prolonged chemotherapy. This group is made up of patients with stage IV disease that involves distant organs such as the brain, liver and bowel. Specially designed chemotherapy treatments using drugs that have been shown to be effective against other cancers are being employed to prolong life for many of these women.

• #96

  https://journals.lww.com/greenjournal/fulltext/2021/02000/gestational_trophoblastic_disease__current.22.aspx

  The most frequently used single-agent regimens with methotrexate and actinomycin D are listed in Table 4. […] Patients with a FIGO risk score of 7 or higher should initially be treated with aggressive multiagent chemotherapy; surgery or radiation or both are often incorporated into treatment. […] Multiagent regimens incorporate etoposide, with or without cisplatin, into cyclical combination chemotherapy with high rates of success and lower acute toxicity. […] Treatment of high-risk gestational trophoblastic neoplasia that is resistant to initial chemotherapy is challenging. […] Chemotherapy is continued until hCG values have normalized, and this is followed by at least two to three courses of consolidation chemotherapy for the purpose of eradicating all viable tumor. […] After hCG remission has been achieved, patients with gestational trophoblastic neoplasia should be managed with serial determinations of hCG levels at 2-week intervals during the first 3 months of remission and then at monthly intervals for at least 12 months.

• #97 Gestational Trophoblastic Neoplasia Treatment & Management: Medical Care, Surgical Care, Prevention

  https://emedicine.medscape.com/article/279116-treatment

  A gynecologic oncologist experienced in managing GTN should be consulted. Patients with resistant disease may benefit from consultation at a regional trophoblastic disease center. […] A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the total number of chemotherapy cycles needed to achieve remission. Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases. A repeat DC in the presence of persistent tissue on pelvic ultrasonography may reduce the number of chemotherapy cycles needed to achieve remission. Craniotomy may be needed to control bleeding and provide decompression. Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission.

• #98

  https://journals.lww.com/greenjournal/fulltext/2021/02000/gestational_trophoblastic_disease__current.22.aspx

  This review summarizes the current evaluation and management of gestational trophoblastic disease, including evacuation of hydatidiform moles, surveillance after evacuation of hydatidiform mole and the diagnosis and management of gestational trophoblastic neoplasia. […] It is important to individualize treatment based on their risk factors, using less toxic therapy for patients with low-risk disease and aggressive multiagent therapy for patients with high-risk disease. Patients with gestational trophoblastic neoplasia should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients. […] The primary treatment for most forms of gestational trophoblastic neoplasia is chemotherapy, based on the individual patients risk. […] Primary remission rates of patients treated for low-risk gestational trophoblastic neoplasia are high using a variety of chemotherapy agents.

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