Recurrent Gestational Trophoblastic Neoplasia Research Articles

Evaluation of efficacy and safety of chemotherapy in the treatment of recurrent or resistant gestational trophoblastic neoplasia: A protocol for systematic review and meta-analysis.

Background:Gestational Trophoblastic Neoplasia (GTN) is a spectrum of pregnancy-associated tumours emerging from placental tissue. Generally, GTN patients are considered to have a high rate of recovery. However, almost 25 per cent of GTN tumours resist, or have a high probability of relapsing following the first line of chemo treatment. Thus, tumours that resist or relapse requires salvage chemotherapy, sometimes accompanied by surgery. Globally, clinicians utilize a range of salvage regimens. Currently, ongoing debates are centred around choosing the best regimens in terms of safety and efficacy. Therefore, the current research aims to appraise the success and level of safeness using chemotherapy to treat patients with resistant or recurrent GTN.Methods:The authors will conduct a methodological exploration in online-based databases to find Randomized Controlled Trials related to the adoption of chemotherapy agents as treatment for resistant or recurrent GTN patients. The databases are as follows: EMBASE, PubMed, Cochrane Database Central, UpToDate, Chinese National Knowledge Infrastructure, Web of Science, and WanFang Database. The search will be limited to articles published in either English or Chinese. Moreover, the authors will also perform a search for ongoing trials on online-based clinical trial registries. Two independent authors will screen and select articles for review. A similar process will be followed by two independent authors to complete the extraction of data and evaluate the bias risk. In relevant cases, the authors will contract trial investigators to obtain related, unpublished data. The authors will use the random-effects model for pooling data in RevMan software (v5.3).Results:The present systematic review aims to evaluate the efficacy and level of safeness associated with using chemotherapy for resistant or recurrent GTN patients.Conclusion:The results of the proposed systematic analysis could summarize the most recent evidence for the use of chemotherapy agents on GTN patients.Ethics and dissemination:Since the proposed study uses pre-published data, an ethical approval is not required.Review registration number:Aug 25, 2021.osf.io/rgzbn. (https://osf.io/rgzbn/).

Diagnosis and Management of Gestational Trophoblastic Disease: A Comparative Review of National and International Guidelines.

Gestational trophoblastic disease (GTD) is associated with increased mortality and morbidity in women of reproductive age, if managed in a suboptimal way, left untreated, or diagnosed after the development of extensive metastases. The aims of this study were to review and compare the recommendations from published guidelines on these tumors of placental origin. A descriptive review of guidelines from the Royal College of Obstetricians and Gynecologists, the International Federation of Gynecology and Obstetrics, the European Society for Medical Oncology, and the Royal Australian and New Zealand College of Obstetricians and Gynecologists on GTD was carried out. All the guidelines agree that suction evacuation is the optimal management for hydatidiform molar pregnancy and that chemotherapy, either single-agent (for low risk) or multiagent (for high risk), is the preferred treatment modality for choriocarcinoma. There is also a consensus that a future pregnancy should be avoided during follow-up; therefore, an effective contraception method should be used. All medical societies recommend the registration of such patients to GTD screening centers, endorse the use of International Federation of Gynecology and Obstetrics 2000 scoring system, and mention that the diagnosis of gestational trophoblastic neoplasia (GTN) should be based on the clinical presentation (from the genital tract and the metastatic sites) and the human chorionic gonadotropin evaluation. Additionally, all 4 medical societies recommend the surgical management of placental site trophoblastic tumors or epithelioid trophoblastic tumors, as chemotherapy is less effective in these cases. However, there is controversy regarding the appropriate follow-up after the treatment of hydatidiform mole, the administration of anti-D immunoglobulin, the time of oxytocin infusion, and the salvage regimens that may be used in cases of resistant or recurrent GTN. There is need for consistent international practice protocols, which will lead to an earlier diagnosis and eventually to a more effective management of GTD worldwide and decrease in the recurrence rate and in the associated morbidity and mortality.

Preliminary study of PD-1 inhibitor in the treatment of drug-resistant recurrent gestational trophoblastic neoplasia

Objective: To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN). Methods: Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed. Results: (1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment. Conclusions: PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Management and risk factors of recurrent gestational trophoblastic neoplasia: An update from 2004 to 2017.

ObjectiveWe investigated the clinical characteristics, treatments, and survival of patients with gestational trophoblastic neoplasia (GTN) who experienced recurrence. Factors predictive of recurrence were also investigated.MethodsPatients with GTN who recurred after completing chemotherapy at Peking Union Medical College Hospital Trophoblastic Disease Center were identified between January 2004 and December 2017. Logistic regression analysis was used to identify factors predictive of GTN recurrence.ResultsA total of 1827 patients with GTN achieved complete remission (CR) at our center, of whom 118 (6.5%) experienced recurrence during follow‐up. The recurrence rates for patients initially treated at our center and those referred to us were 2.7% and 14.6%, respectively. The majority of recurrent patients received floxuridine‐based multiagent chemotherapy (n = 64). Patients who underwent surgery achieved a significantly higher CR rate than those who did not (88.6% vs 61.1%, P = .001). Although 94.1% of recurrent patients reachieved CR, 33.3% of them recurred for a second time. The 5‐year survival rate of the entire cohort was 80.4%. An interval between antecedent pregnancy and chemotherapy >12 months (OR: 6.600, 95% CI [3.217‐13.540], P < .001), and an interval from first chemotherapy to achieving β‐human chorionic gonadotropin (β‐hCG) normalization >14 weeks (OR: 2.226, 95% CI [1.080‐4.588], P = .030) were predictors of recurrence.ConclusionsPatients with recurrent GTN are prone to recurring for a second time. Surgery plays a beneficial role in the management of recurrent GTN. An interval between antecedent pregnancy and chemotherapy >12 months, and an interval from first chemotherapy to achieving β‐hCG normalization >14 weeks were predictors of recurrence.

Application of chest CT scan in gestational trophoblastic neoplasia with lung metastasis

Objective: To explore the role of CT scan for the diagnosis of lung metastasis in stage Ⅲ gestational trophoblastic neoplasia (GTN) . Methods: To figure out the role of CT scan for lung metastasis in GTN initial diagnosis, treatment and follow-up, 93 GTN patients with lung metastasis from January, 2015 to December, 2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients with the International Federation of Gynecology and Obstetrics (FIGO) score ≤6 were defined as low risk GTN and 23 patients score score ≥7 were defined as high risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with pulmonary lesions were identified both by chest X-ray compared to CT scan. Five cases were excluded due to no consensus could make for the results of chest X-ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70) in low risk GTN and 43% (10/23) in high risk GTN patients without statistical difference (χ(2)=0.090, P=0.925) . For those patients with positive chest CT scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen (35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray results due to the lower sensitivity compared to CT scan. (2) In 88 patients with stage Ⅲ, 78 patients had successful initial treatment, but 4 of them were recurrence in twelve months follow-up. Ten patients were chemotherapy resistance for the initial treatment. The initial chemotherapy remission rate in low risk GTN patients was higher than that in high risk ones (χ(2)=4.911, P=0.027) . In 49 cases with negative chest X-ray, there was no correlation with the rate of remission,chemotherapy resistance and recurrence in stage Ⅲ patients (P>0.05) . (3) For those patients who had poorly response to initial chemotherapy, the diameters of lesions in lung were unchanged or increased during the treatment, form (5.1±4.1) mm to (7.4±2.8) mm. The pulmonary lesions were continuously shrunk from (7.8±5.3) mm to (4.7±4.4) mm for those patients with complete and partial remission including the recurrent GTN patients (Z=-2.713, P=0.007) . Conclusions: Patients with GTN in stage Ⅲ have down staging if only use chest X-ray for imaging at the initial diagnosis. Chest CT scan is recommended for primary imaging evaluation of FIGO staging in qualified medical organization. For those patients with persistent abnormal serum hCG level and negative chest X-ray, chest CT scan is strongly recommended to identify the persist or resistant lung lesions and follow up.

Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

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. To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials. Only randomised controlled trials (RCTs) were included. We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. The search identified no RCTs; therefore we were unable to perform any meta-analyses. RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. 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.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 (5-FU), 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. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.

Treating gestational trophoblastic disease

Importance of the field: Gestational trophoblastic disease is one of the few human malignancies that is curable, even in advanced stages of the disease. However, appropriate management and follow-up are essential components in curing this disease.Areas covered in this review: Observational, retrospective and prospective studies evaluating the efficacy of medical and surgical management of gestational trophoblastic disease were analyzed to provide a comprehensive review of current and new treatment modalities. We searched PubMed, Medline and the Library of Congress from January 1965 to January 2010.What the reader will gain: The reader will obtain information on how to classify gestational trophoblastic neoplasia (GTN) into low- and high-risk groups, as well as learn the medical and surgical management of low- and high-risk GTN and recurrent GTN. The effectiveness of treatment regimens and subsequent fertility is also reviewed.Take home message: GTN is highly responsive to chemotherapy. However, surgery is an important adjunct in select cases. Even in advanced-stage or recurrent disease, cure can be achieved and fertility preserved.

Methotrexate, Bleomycin, and Etoposide in the Treatment of Gestational Trophoblastic Neoplasia

The combination of methotrexate (1 g/m(2) day 1), bleomycin (10 mg day 3), and etoposide (100 mg/m(2) days 1-5) (MBE) has been used for disease relapse or as a second-line chemotherapy in the treatment of gestational trophoblastic neoplasia (GTN) resistant to multiple-agent chemotherapy. With the identification of ultra-high-risk GTN, MBE has also been used as first-line chemotherapy. The current study is to review the use of MBE in the treatment of GTN. Patients who received MBE for GTN between 1985 and 2003 in Queen Mary Hospital were included in this study. Records were reviewed and data were analyzed. Outcomes including response rate, treatment complications, and survival were assessed. Methotrexate, bleomycin, and etoposide therapy was given as first line to 4 patients with ultra-high-risk GTN. Three responded to the treatment and remained disease free. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who had drug resistance to the initial therapy. Seven responded, and 6 remained disease free at 5 years. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who relapsed 2-18 months after their initial therapy. Seven patients responded, and 4 remained disease-free at 5 years, 2 defaulted, and one died of carcinoma of the colon. Of the 20 patients who received MBE, 12 developed grade 3/4 neutropenia, and 4 developed grade 3/4 thrombocytopenia. The overall response rate for MBE was 85%. Methotrexate, bleomycin, and etoposide should be considered as a second-line therapy in patients who have drug-resistant or recurrent GTN.