Low-risk Gestational Trophoblastic Neoplasia Research Articles

Upfront Hysterectomy Versus Primary Chemotherapy in the Management of Low-Risk Gestational Trophoblastic Neoplasia at Old Age Patients: A Prospective Study

Upfront Hysterectomy Versus Primary Chemotherapy in the Management of Low-Risk Gestational Trophoblastic Neoplasia at Old Age Patients: A Prospective Study

Removal of an Intrauterine Polypoid Lesion Resolved Chemotherapy-resistant Gestational Trophoblastic Neoplasia: A Case Report.

Single-agent chemotherapy typically has curative outcomes in patients with low-risk gestational trophoblastic neoplasia (GTN). Although surgical intervention is a potential alternative, its efficacy in these patients remains unclear. This report describes a case in which surgical excision of a uterine polypoid lesion resolved chemotherapy-resistant low-risk GTN. A 43-year-old patient received pulse actinomycin D treatment for post-molar low-risk GTN without extrauterine metastasis. However, the patient showed resistance to the chemotherapy regimen. There was no initial evidence of protrusion of GTN into the uterine cavity; however, a polypoid lesion grew into the uterine cavity during therapy. This growth was successfully excised via a transvaginal approach using forceps with minimal blood loss. There was a postoperative decrease in human chorionic gonadotropin levels, which ultimately reached the predetermined threshold without the need for changing the therapeutic protocol. Surgical resection should be considered a viable therapeutic strategy for uterine polypoid growth in chemotherapy-resistant low-risk GTN.

First-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia: a network meta-analysis.

The efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). Databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case-control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint. Twenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30-50 mg/m2) in RCT. Among the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies.

Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

Efficacy and Safety of the Surgery-First Approach Compared to the Chemotherapy-First Approach for Treating Low-Risk Gestational Trophoblastic Neoplasia: A Systematic Review and Meta-Analysis.

For gestational trophoblastic neoplasia (GTN) affecting women of reproductive age, the chemotherapy-first approach is often preferred over the surgery-first approach. Low-risk GTN is treated with a chemotherapy-first approach, but the number of courses required can affect fertility. A surgery-first approach may decrease the number of chemotherapy courses, but its efficacy and safety compared to a chemotherapy-first approach are unclear. Thus, we investigated the efficacy and safety of the surgery-first approach compared to the chemotherapy-first approach in treating low-risk GTN. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases for relevant articles in July 2023. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. The primary outcomes were remission, the mean number of chemotherapy courses required to cure, and adverse events. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study protocol was registered in the Open Science Framework (https://osf.io/kysvn/). Studies for low-risk GTN included a qualitative synthesis (with 2,192 participants and ten studies, eight of which were about second uterine curettage and two about hysterectomy) and a meta-analysis (with 138 participants and two randomized controlled trials (RCTs) that compared first-line treatments of second uterine curettage and chemotherapy). Second uterine curettage may result in little to no difference in remission (risk ratio: 1.00, 95% confidence interval: 0.96-1.05; low certainty) and a slight reduction in adverse events (risk ratio: 0.87, 95% confidence interval: 0.47-1.60; low certainty). The evidence is very uncertain on the mean number of chemotherapy courses (mean difference: 2.84 lower, 95% confidence interval: 7.31 lower to 1.63 higher; very low certainty). Based on clinical outcomes, second uterine curettage can be comparable to the chemotherapy-first approach as a first-line treatment option for low-risk GTN; however, the overall certainty of the evidence was low or very low.

Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0–4): study protocol for a prospective, multicentre, randomized trial

BackgroundSingle-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens.MethodsWe will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0–4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life.DiscussionPrevious clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia.Trial registrationClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020–9-24, version 1.0).

Efficacy analysis of single-agent carboplatin AUC4 2-weekly as second-line therapy for methotrexate-resistant (MTX-R) low risk gestational trophoblastic neoplasia (GTN)

BackgroundApproximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0–6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC. Updated results for carboplatin demonstrate an 86% complete hCG response (hCG CR) but associated with haematological dose-limiting toxicity. MethodsIn 2017, single-agent carboplatin became the national standard second-line treatment following MTX-R at hCG of >3000 IU/L. Carboplatin was changed to two-weekly AUC4 scheduling and continued until normal hCG plus 3 consolidation cycles. For patients failing to respond, CC (Etoposide-Actinomycin-D or EMA-CO) was introduced. Results22 evaluable patients with a median hCG at MTX-R of 10,147 IU/L (IQR 5527–19,639) received carboplatin AUC4 2-weekly (median no. of cycles = 6, IQR 2–8). Of these, 36% achieved a hCG CR. All 14 non-CR patients were cured with subsequent CC; 11 and 2 patients with 3rd line and 4th line CC respectively and 1 patient following 5th line CC and hysterectomy. Overall survival remains 100%. ConclusionCarboplatin is not sufficiently active in the second-line treatment of low-risk MTX-resistant GTN. New strategies are required to increase hCG CR and spare more toxic CC regimens.

Effect of actinomycin D on ovarian reserve in low-risk gestational trophoblastic neoplasia

ObjectiveThis study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy.MethodsThis study recruited premenopausal women aged...

Repeat Curettage In the Management of Low-Risk Gestational Trophoblastic Neoplasia (GTN).

Repeat Curettage In the Management of Low-Risk Gestational Trophoblastic Neoplasia (GTN).

Gestational Trophoblastic Neoplasia—A Retrospective Analysis of Patients Treated at a Tertiary Care Oncology Center in North India

Objectives The aim of this study was to do a retrospective analysis of patients of gestational trophoblastic neoplasia (GTN) treated at our center concerning their clinical features and treatment outcomes. Materials and Methods Patients diagnosed and treated from May 2018 to December 2021 were included. All relevant information pertaining to eligible patients was retrieved from the electronic medical records. Patients were risk-stratified based on the World Health Organization (WHO) risk scoring system with a score of seven and above being classified into the high-risk category. Patients were monitored for response by measuring β-human chorionic gonadotrophin (β-HCG) levels before each consecutive cycle. Statistical Analysis Appropriate statistical analysis was performed using SPSS version 26. Results Records of 39 eligible patients were analyzed for clinical features out of which 38 were eligible for response assessment. The median age of presentation was 28 years with the majority of patients (79.4%) diagnosed based on β-HCG levels and clinical history alone. The most common symptom was bleeding per vagina (64%), while the majority of antecedent pregnancies were abortions (59%).Of the 14 low-risk category patients, 12 received single-agent methotrexate/actinomycin D, while 2 received etoposide, methotrexate actinomycin D (EMACO) regimen. Overall response rates were 85.7% with the others responding to the second-line EMACO regimen. Five patients in this group had a WHO score of 5 or 6 and all of them responded to single-agent treatment. Among the 25 high-risk category patients, all received the EMACO regimen with high-dose methotrexate added to those with brain metastasis. The response rate was 87.5% with all the nonresponders having features of ultra-high risk of liver/brain metastasis and/or a WHO score of more than 12. While one nonresponder had expired despite treatment, the other two responded to the etoposide methotrexate and actinomycin D/ etoposide and cisplatin regimen. Conclusion Our results are in consonance with other reported studies. The subcategories of low-risk GTN with a WHO score of 5 and 6 and high-risk GTN with ultra-high-risk features deserve further research in the form of multicenter prospective studies.

5 Fluorouracil as firs t line treatment for low risk gestational trophoblastic neoplasia

Purpose: To investigate the efficacy and prognostic factors in response to 5-fluorouracil (5-FU) in lowrisk gestational trophoblastic neoplasia (GTN).Methods: This single-center retrospective study analyzed the hospital records of 204 LRGTN patients admitted to Department of Gynecology, Liaoning Cancer Hospital &amp; Institute of China from 2002 to 2016 for retrieval of their clinical data, chemotherapy regimens, related side-effects, and evaluation of treatment efficacy and prognostic factors.Results: The median progression-free survival (PFS) was 55 months (3 - 190 months). The overall cure rate was 100 %, with no tumor-related deaths. When a single-agent regimen i.e. 5-FU, was selected for initiation of treatment for 132 patients while only 49 of them were treated with chemotherapy, the effective cure rate was 62.88 % (83/132); while the overall drug resistance r was 27.27 % (36/132). For patients with FIGO scores ≥ 4 points, the incidence of drug resistance was 71.43 % (5/7), while the incidence of III/IV myelosuppression was 10.61 % (14/132). A total of 38 patients (18.63 %) received surgical treatment in addition to chemotherapy. A comparison was made between two groups of patients with non-drug resistance, i.e., patients with unexpected GTN diagnosed postoperatively and those who received chemotherapy preoperatively. It was found that the number of courses of GTN chemotherapy for those who were unexpectedly diagnosed postoperatively was more than that for those who received chemotherapy preoperatively (p = 0.004).Conclusion: The single drug (5-FU) was effective in the management of low-risk (LR)-GTN. Treatment failure was related to drug resistance, high tumor score, and severe toxicity. Multi-agent regiments in combination with surgery, were an effective treatment method for GTN. For patients without metastasis and fertility requirements, surgery after chemotherapy significantly shortened the treatment cycle without increasing complications.

Single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Low-risk gestational trophoblastic neoplasia could be cured in the case of appropriate management with single-agent chemotherapy. This study was carried out to compare the efficacy of single-dose methotrexate versus Actinomycin-D in low-risk gestational trophoblastic neoplasia to analyze the most effective agent. This retrospective cohort study was conducted on the medical record of 170 cases with the diagnosis of low-risk gestational trophoblastic neoplasia from 2012 to 2019 to evaluate the response rate of single-dose weekly-methotrexate versus biweekly-Actinomycin-D. Single agent chemotherapy was required in 170 patients with final risk score of less than 7. Among the 100 cases under weekly-methotrexate therapy, 29 patients were required second-line chemotherapy with Actinomycin-D and combination therapy which means complete remission of 71% with methotrexate, in comparison with 78.5% in the other group. Resistance was mostly seen in patients with documented choriocarcinoma in histology who had not received timely diagnosis and treatment. Individualized decision in the management of low-risk gestational trophoblastic neoplasia cases, based on histology, HCG, and history is the corn stone in successful treatment.

Resistance to single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Methotrexate (MTX) and actinomycin D (ActD) have been used as first-line chemotherapy agents in the treatment of low-risk gestational trophoblastic neoplasia (GTN). Although low-risk GTN is considered a curable disease, its reported primary remission rates of 49 to 93% reflect the difficulties of treatment and different factors influencing it. Hence, this study aimed to determine the remission rates and related factors of single-agent chemotherapy resistance in low-risk GTN patients. This retrospective study included patients with diagnosed low-risk GTN who received either MTX once a week (IM, 30mg/m2) or ActD once every two weeks (pulsed IV, 1.25mg/m2). Then, the patients were followed-up until complete remission or single-agent treatment failure to assess resistance rate and related factors. Eighty-four patients were included in the study (18 patients were receiving MTX and 66 patients were receiving ActD). 85.7% of all participants achieved complete remission after first-line chemotherapy (72.2% in MTX vs 89.4% in ActD). There was a significant association for higher tumor size (P=0.046), the occurrence of metastasis (P=0.019), and pretreatment β-HCG levels (P=0.005) with resistance to treatment. This study demonstrated higher tumor size, the occurrence of metastasis, and pretreatment β-HCG levels have been associated with increased resistance to first-line chemotherapy agents.

Long-term outcome of ultrasound-guided focused ultrasound ablation for gestational trophoblastic neoplasia in the cesarean scar: a case report

BackgroundThe treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility.Case presentationA 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up.ConclusionUltrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding.

Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia

BackgroundSingle-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse. MethodsBetween January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5–6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR. ResultsIn LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5–6 patients. The incidence of MTX toxicity was not influenced by BSA or weight. ConclusionsIn the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.

Predicting Chemotherapy Resistance in Gestational Trophoblastic Neoplasia: Ratio of Neutrophils, Lymphocytes, Monocytes, and Platelets.

BACKGROUND Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) have recently been used as inflammatory biomarkers for cancer patients. This study aims to determine the role of pretreatment NLR, LMR, and PLR in predicting chemoresistance in gestational trophoblastic neoplasia (GTN) patients. MATERIAL AND METHODS A total of 129 low-risk and high-risk GTN patients who had received first-line chemotherapy were enrolled in this historical cohort study. The pretreatment NLR, LMR, and PLR values were analyzed to predict the resistance to first-line chemotherapy in low-risk and high-risk GTN patients. RESULTS Chemoresistant patients had significantly higher NLR than chemosensitive patients in low-risk and high-risk GTN patients (P<0.05). In high-risk GTN, patients with lower LMR and higher PLR tended to have chemoresistance to first-line chemotherapy (P=0.008, P=0.001). Univariate analysis revealed that the NLR, LMR, and PLR cut-off points of 2.654, 3.8, and 192.174, respectively, were associated with chemoresistance in high-risk GTN (P=0.0001, P=0.011, P=0.0001). The combination of NLR, PLR, and FIGO score in high-risk GTN was the best combination among other combinations with cut-off value >17 (P=0.001). CONCLUSIONS Higher NLR, lower LMR, and higher PLR were associated with chemoresistance for high-risk GTN patients. Furthermore, NLR, LMR, and PLR can improve the accuracy of predicting resistance to first-line chemotherapy in high-risk GTN.

Monotherapy for low-risk gestational trophoblastic neoplasia with score 5-6.

To investigate the monotherapy for gestational trophoblastic neoplasia (GTN) patients with FIGO/WHO prognostic score of 5-6. The low-risk GTN patients from 2012 to 2019 were enrolled. The study is a retrospective report to analyze the efficacy and safety of single-agent chemotherapy and combination chemotherapy in patients with a high FIGO/WHO prognostic score of 5-6. 75 cases (33.5%) were included. Complete remission was in all patients. Among the 29 cases taking single-agent chemotherapy, 22 cases (75.9%) developed drug resistance. Among the 46 cases taking combination chemotherapy, 7 patients (15.2%) developed drug resistance. There was a statistically significant difference in the drug resistance rate between these two subgroups (P < 0.05), but there was not statistically significant difference in the total number of chemotherapy courses (<2mIU/ml) (P < 0.05). Monotherapy showed remarkable advantages in GTN patients with FIGO/WHO prognostic score of 5-6.

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia.

There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p = 0.019). 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Current Evidence on Immunotherapy for Gestational Trophoblastic Neoplasia (GTN).

Simple SummaryGestational trophoblastic neoplasia (GTN) is a rare tumor group that arises from the malignant transformation of placental tissue. Based on the evaluation of International Federation of Gynecology and Obstetrics (FIGO) anatomic staging and FIGO prognostic score, GTN is divided into low-, high-, and ultra-high-risk groups if the score obtained is less than or equal to 6, greater than 6 or greater than 12, respectively. The standard treatment is chemotherapy, using a single agent in low-risk disease and multiagent chemotherapy in high- and ultra-high-risk GTN. In chemoresistant forms of GTN, the use of immune checkpoint inhibitors, such as anti-PD-1 or anti-PD-L1/2, could represent a new therapeutic strategy. In this study, we evaluate the available evidence on immune checkpoint inhibitors for GTN treatment.Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

Comparing and Evaluating Five-Day Chemotherapy Agents Actinomycin D and Methotrexate in Low-Risk Post-Molar Gestational Trophoblastic Neoplasia: A Retrospective Analysis

Background: Low-risk post-molar gestational trophoblastic neoplasia is sensitive to chemotherapy, but there is no consensus regarding the best treatment regimen for low-risk post-molar gestational trophoblastic neoplasia. This study aimed to assess the efficacy, toxicity and cost-effectiveness of actinomycin D and methotrexate in low-risk post-molar gestational trophoblastic neoplasia. Methods: 210 patients with Federation International of Gynecology and Obstetrics(FIGO)-defined low-risk post-molar gestational trophoblastic neoplasia received either a first-line five-day methotrexate intramuscular injection biweekly (MTX group) or a five-day actinomycin D infusion biweekly (Act-D group). Demographic information, disease manifestations, initial treatment plan, treatment-related adverse events, cost-effectiveness and the effects of drugs on ovarian function and quality of sexual life were recorded and retrospectively compared. Results: The complete response rates were 72.73% for the Act-D group and 75.41% for the MTX group, with no statistically significant difference. Compared to the Act-D group, the MTX group had a significantly shorter total number of chemotherapy cycles and average hospitalization expenses (p &lt; 0.05). There was no severe adverse effect reported for either group, but the Act-D group was associated with significantly higher leukopenia (grade 1 or 2) (59.38% vs. 17.39%). The two regimens had reversible effects on ovarian function and quality of sexual life, but there was no significant difference between the two groups. Conclusions: There were similar complete response rates and no severe adverse effect reported for either group, but the total treatment course was shorter and the average hospitalization expenses were lower in the MTX group. Five-day MTX intramuscular biweekly injections remain the treatment of choice for patients with low-risk post-molar gestational trophoblastic neoplasia. Chemotherapy will have a certain impact on ovarian function. Gynecological oncologists should pay attention to the protection of ovarian function in patients with gestational trophoblastic neoplasia during perioperative chemotherapy.