Treatment Of Gestational Trophoblastic Neoplasia Research Articles

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.

Effect of lung metastasis on the treatment and prognosis of patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle-Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta-analysis was performed using Stata 12.0 and GradePro software. Five publications with 3629 GTN patients were included. The meta-analysis revealed that the GTN with lung metastasis was strongly correlated with first-line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease-specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease-specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high-risk factor for prognosis of GTN and deserves more attention in the choice of first-line chemotherapy regimens and follow-up.

Patients' experience of menopausal symptoms post-chemotherapy treatment for gestational trophoblastic neoplasia

PurposeWe aimed to explore patient's experience of chemotherapy-induced menopausal symptoms; to ascertain how patients tried to alleviate their symptoms and how health professionals supported them in order to identify current unmet needs. MethodsWe designed a retrospective cross-sectional exploratory study of a sample of 11 women who received multi-agent combination chemotherapy for Gestational Trophoblastic Neoplasia. Postal surveys using the Greene Climacteric Scale (GCS) questionnaire followed up by semi-structured telephone interviews were used. Framework analysis technique was used to generate descriptions of patient's experiences. ResultsSymptoms of feeling tired or lacking in energy, loss of interest in sex, muscle and joint pains and difficulty in concentrating affected participants the most. The menopausal symptoms appear to be temporary; symptoms such as hot flushes and night sweats seem to subside with resumption of menses. Others are more gradual with some evidence that mental health takes longer to recover. Regarding potential symptoms, some women do not retain the information given to them at discharge following end of treatment, which GTD services need to take into consideration when supporting patients. ConclusionPatients need to be more optimally prepared for post-chemotherapy recovery with each patient's needs and support being individually tailored. How information is discussed and disseminated needs improving to ensure patients retain the information they receive at discharge. Recommendations include the creation of menopause information booklet, alongside further developing virtual nurse-led follow up clinics post chemotherapy.

Low‐risk gestational trophoblastic neoplasia – 20 years experience of a state registry

BackgroundGestational trophoblastic disease (GTD) is an uncommon but highly treatable condition. There is limited local evidence to guide therapy.AimsTo report the experience of a statewide registry in the treatment of low‐risk gestational trophoblastic neoplasia (GTN) over a 20‐year period.Materials and MethodsA retrospective review of the prospectively maintained GTD registry database was conducted. There were 144 patients identified with low‐risk GTN, of which 115 were analysed. Patient demographics, treatment details and outcomes, including development of resistance, toxicity or relapse were reviewed.ResultsThe incidence of GTD was 2.6/1000 live births. There was 100% survival. The mean time from diagnosis to commencing treatment was 1.9 days (range 0–29 days). Seventy‐seven percent of patients treated with methotrexate achieved complete response. Thirteen patients (11.3%) required multi‐agent chemotherapy, for the treatment of resistant or relapsed disease. There was a higher rate of treatment resistance in those with World Health Organization (WHO) risk scores 5–6 (odds ratio (OR) 6.56, 95% CI 1.73–24.27, P = 0.005) and those with pre‐treatment human chorionic gonadotropin &gt;10 000 (OR 4.00 95% CI 1.73–24.27 P = 0.007). Four patients (3.5%) were diagnosed with choriocarcinoma after commencing treatment. Nine patients (7.8%) had successful surgical treatment for GTN, both alone and in combination with chemotherapy. The relapse rate was 4.3%; all were treated successfully with a combination of chemotherapy and surgery, and 93.9% of patients completed follow up through the registry.ConclusionsMethotrexate is a highly effective treatment for low‐risk GTN, especially with WHO risk score ≤4. The optimal treatment for those with risk scores of 5–6 requires further investigation.

Second curettage versus conventional chemotherapy in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses for patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

Chemotherapy is the recommended treatment for gestational trophoblastic neoplasia (GTN). Second curettage had been advocated to avoid unnecessary chemotherapy and to reduce the courses of chemotherapy; however, consensus has not been reached as there are arguments claiming its inability of inducing complete regression. The present study was performed to clarify the effectiveness of second curettage for avoiding unnecessary chemotherapy and lowering the number of chemotherapy courses in patients with post-molar GTN. Seven predominant electronic databases were searched, including four English databases and three Chinese databases, from the inception of each database until January 31, 2023. Studies were included if they were: (1) human, (2) explicitly indicated exposure to second curettage, (3) explicitly indicated control to conventional chemotherapy, (4) explicitly indicated the participants were patients with gestational trophoblastic neoplasia (GTN), and (5) compared the outcome of interest as the number of the course of chemotherapy. Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. The data of study location, data collection, study design, number of participants, intervention strategy, control strategy, the follow-up period, outcome, adverse events were analyzed. With regard to avoiding unnecessary chemotherapy, the overall pooled effect size of the second curettage group had a significant advantage over the conventional chemotherapy group with an OR of 0.02 (95% CI: 0.00-0.06). Meanwhile, for reducing the number of chemotherapy courses, the overall pooled effect size of the second curettage group had significant advantage over the conventional chemotherapy group with a mean difference of -2.11 (95% CI: -3.72 to -0.51). The second curettage group had a significant advantage over the conventional chemotherapy group in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses. Further larger multi-center randomized controlled trials should be conducted to confirm our results and to clarify the optimal patients' group for second curettage in patients with post-molar GTN.

Synchronous placental site trophoblastic tumor and choriocarcinoma

Link of Video Abstract: https://youtu.be/bx7KdiTKiOQ Introduction: Gestational trophoblastic neoplasia (GTN) comprises a series of malignancies characterized by abnormal proliferation of fetal trophoblastic tissue. GTN lesions refer to a class of malignant lesions that have distinct histopathologic features, including invasive hydatidiform moles, choriocarcinomas, placental site trophoblastic tumors (PSTT), and epithelioid trophoblastic tumor (ETT). Most often, they occur coexist separately, but there are also cases of mixed GTN with a combination of histologic PSTT, ETT, or choriocarcinoma. PSTT is a rare form of gestational trophoblastic disease (GTD). The percent incidence of this disease is 0.23% of total GTD and 1-2% of total GTN. The incidence rate of choriocarcinoma is also limited. Data collection on the incidence of mixed GTN has been more challenging due to the rarity of this disease. Case Description: We report a case of a 26-year-old female patient with choriocarcinoma and PSTT. The patient’s beta-human chorionic gonadotropin (β-hCG) levels remained elevated despite treatment with single-agent chemotherapeutic regimen. She underwent a series of chemotherapy treatments and two surgeries were required. The histological examination of the uterine tumor revealed a choriocarcinoma whilst the hysterectomy thereafter showed a PSTT. After the hysterectomy the β-hCG level continued to rise. Due to chemotherapy resistance, EMACO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) was changed to EP-EMA (Etoposide, cisplatin, etoposide, methotrexate, actinomycin-D). After two administrations of EP-EMA, β-hCG levels normalized. Conclusion: This is a rare case of mixed GTN of choriocarcinoma and PSTT. Mixed GTN should be considered when chemotherapy is not effective in the treatment of GTN. These cases need to be reported to improve the diagnosis and management of patients.

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.

EMACO for treatment of gestational trophoblastic neoplasia: A multinational multicenter study

ObjectiveTo investigate the efficacy and toxicity of etoposide, methotrexate, actinomycin D alternating with cyclophosphamide, and vincristine (EMACO) for treatment of gestational trophoblastic neoplasia, and for factors independently associated with EMACO resistance and disease-specific death in an international cohort. MethodsMedical records of GTN patients who received EMACO during 1986–2019 from gestational trophoblastic disease centers from four countries including the USA, Thailand, Hungary, and Brazil, were retrospectively reviewed. Among 335 GTN patients, 266 patients who received EMACO as primary chemotherapy were included in the primary treatment group, and 69 patients who received EMACO after relapse/resistance to single-agent chemotherapy were included in the prior treatment group. ResultsThree-quarters (76.1%) of all patients achieved remission, and the survival rate was 89%. The prior treatment group had better outcomes than the primary treatment group relative to remission rate (87.0% vs. 73.3%, p = 0.014) and number of EMACO cycles to achieve remission (3 vs. 6 cycles, p < 0.001). Sustained remission increased to 87.2% in EMACO-resistant patients treated with later-line chemotherapy. Number of metastatic organs ≥2 (adjusted odds ratio [aOR]: 2.33, p = 0.049) was the only independent predictor of EMACO resistance among overall patients. Interval from index pregnancy ≥7 months (aOR: 4.34, p = 0.001), and pretreatment hCG >100,000 IU/L (aOR: 2.85, p = 0.028) were independent predictors of EMACO resistance in the high-risk subgroup. The only factor independently associated with disease-specific death was EMACO resistance (aOR: 176.04, p < 0.001). ConclusionsEMACO is an effective treatment for GTN. Number of metastatic organs and EMACO resistance were the independent predictors of EMACO resistance and disease-specific death, respectively.

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.

Gestational Trophoblastic Neoplasia: A Clinico-Epidemiological Profile In A Tertiary Care Hospital

Introduction: Gestational trophoblastic neoplasia (GTN) is a group of interrelated lesions that results from abnormal proliferation of placental trophoblastic cells. Early diagnosis and treatment of GTN results in successful outcomes with fertility preservation.This study was intended to stratify GTN cases using WHO scoring system, to diagnose and manage cases as per protocol and to identify complications of treatment of GTN.&#x0D; Methodology: This was a single center prospective observational study conducted at Medical college Kolkata from June 2017 to December 2018. All the diagnosed cases of GTN fulfilling the inclusion criteria were incorporated in the study, data were collected from history, clinical examination and investigations. All the data were tabulated and analyzed by standard statistical methods&#x0D; Results: In this study, primiparous are more prone to have GTN and molar pregnancy was the commonest antecedent event (71.4% of cases). 74.3% (26 out of 35) patients developed disease within four months of previous pregnancy. Anemia and vaginal bleeding were the presenting symptoms in &gt;48.0% cases whereas hemoperitoneum,seizure, hemoptysis and respiratory distress were the rare presenting symptoms.In this study, the cases were diagnosed by histopathology or serial estimation of serum β-hcg. In our study, 91.4% patients were successfully treated with methotrexate and only three cases received EMACO.&#x0D; Conclusion: To conclude this study established that cases of GTN can be successfully treated by early diagnosis and timely management.

Risk Factors That Correlate with Resistance to First-Line Chemotherapy on High-risk Gestational Trophoblastic Neoplasia

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a condition arising from abnormal proliferation of the trophoblastic cells. GTN incidence in Indonesia, precisely in Hasan Sadikin General Hospital, as many as 730 cases are reported per year. GTN is generally highly sensitive to chemotherapy, and multiagent chemotherapy regimens are recommended for high-risk GTN. Multiagent chemotherapy regimens for GTN treatment at Hasan Sadikin General Hospital are EMCO, with no other literature study describing chemotherapy resistance with EMCO today. AIM: This study aimed to identify risk factors associated with first-line chemotherapy resistance at Hasan Sadikin General Hospital. METHODS: In this cross-sectional study, medical records of 81 patients with high-risk GTN presented in the period from January 2018 to June 2021 who received EMCO chemotherapy at Hasan Sadikin General Hospital were retrieved from the archives, and medical data were reviewed and analyzed. Bivariate analysis was performed using the Chi-square test with Fisher’s exact alternative, and multivariate analysis using the binary logistic regression test. p &lt; 0.05 was considered statistically significant. RESULTS: From 81 samples that received EMCO chemotherapy, 15 (18.5%) cases were resistant to EMCO, and 66 (81.5%) cases were responsive to EMCO. The risk factors associated with EMCO resistance were histopathological features and appropriate with EMCO chemotherapy interval (p &lt; 0.05). Variables of age, previous pregnancy, GTN stage, FIGO prognostic score, stage, beta-hCG level, and side effects of EMCO did not significantly correlate with resistance to EMCO (p &gt; 0.05). CONCLUSION: Histopathological features and appropriate chemotherapy intervals were associated with the incidence of resistance to EMCO in Hasan Sadikin General Hospital.

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.

Immune Checkpoint Inhibitors for the Treatment of Gestational Trophoblastic Neoplasia: Rationale, Effectiveness, and Future Fertility.

Most individuals with gestational trophoblastic neoplasia (GTN) are cured with chemotherapy; however, about 5% of them will develop chemotherapy-resistant disease and will die of disease progression. Most GTN tissues express programmed death ligand-1 (PDL-1), making immune checkpoint inhibitors (ICIs) targeting this pathway an attractive treatment option for individuals with GTN. There is increasing evidence to support the use of ICIs for individuals with recurrent or resistant GTN, but available data are derived from case reports and small single arm trials. As promising as it seems, not all individuals with GTN respond to ICIs, and there is lack of evidence toward which factors mediate the effect of ICIs on GTN. In addition, treatment-related adverse events and impact on future fertility are not negligible and should be considered before initiating this treatment. Therefore, additional research is needed to evaluate treatment outcome of ICIs in GTN compared to standard treatment, and to identify molecular and clinical predictors for treatment response, before this treatment is incorporated into the standard of care.

Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia.

Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic neoplasia (GTN). However, the floxuridine, actinomycin D, etoposide and vincristine (FAEV) regimen is commonly used to treat these patients in China. We conducted a randomised controlled trial to compare the efficacies and toxicities of FAEV and EMA/CO. Ninety-four patients with GTN were enrolled between May 2015 and April 2019 and randomly assigned to the FAEV or EMA/CO regimen. The rates of complete remission and relapse and the toxicities were compared in August 2021. Five patients were excluded from the analysis. There were 46 patients in the FAEV group and 43 patients in the EMA/CO group. The complete remission rates following primary treatment were 89.1% and 79.1% (P = 0.193), respectively. The relapse rates were 8.7% and 9.3% (P = 0.604). The apparent incidences of grade 4 myelosuppression were 60.9% and 32.6% (P = 0.008), respectively; however, they became both 32.6% (P = 0.996) after granulocyte colony-stimulating factor support. Other adverse reactions were similar in the two groups. No patient died of disease. FAEV has comparable efficacy and toxicity to EMA/CO as the primary treatment for high-risk GTN, and may thus be another first-line choice of chemotherapy. chictr.org.cn: ChiCTR1800017423.

Results with Floxuridine, Actinomycin D, Etoposide, and Vincristine in Gestational Trophoblastic Neoplasias with International Federation of Gynecology and Obstetrics Scores ≥5.

5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed. Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10-50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived. The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity. The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.

The current situation of health services for hydatidiform mole in Cambodia

Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n=29), provincial hospitals (n=42), district hospitals (n=20), health centers (n=6), and others (n=29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

Improving single-agent chemoresistance risk identification in gestational trophoblastic neoplasia.

In The Lancet Oncology, Antonio Braga and colleagues 1 Braga A Paiva G Ghorani E et al. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study. Lancet Oncol. 2021; (published online June 25.)https://doi.org/10.1016/S1470-2045(21)00262-X Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar report the results of a multicentre, retrospective study involving the largest cohort of patients with gestational trophoblastic neoplasia presenting with an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6, in a low risk setting. 2 Kohorn EI Goldstein DP Hancock BW et al. Workshop report: combining the staging system of the International Federation of Gynecology and Obstetrics with the scoring system of the World Health Organization for trophoblastic neoplasia. Report of the Working Committee of the International Society for the Study of Trophoblastic Disease and the International Gynecologic Cancer Society. Int J Gynecol Cancer. 2000; 10: 84-88 Crossref PubMed Scopus (75) Google Scholar , 3 Goldstein DP Ross S Berkowitz RS Horowitz NS Optimal management of low-risk gestational trophoblastic neoplasia. Expert Rev Anticancer Ther. 2015; 15: 1293-1304 Crossref PubMed Scopus (12) Google Scholar Indeed, in so-called low-risk patients (ie, those with stage I or stage II–III disease and a FIGO risk score of 0–6), patients can have heterogeneous outcomes in terms of chemosensitivity to single-agent chemotherapy; in particular, patients with a FIGO risk score of 0–1 have a complete remission rate of 75% compared with approximately 53% in patients with a FIGO risk score of 2–4 and approximately 33% in patients with a FIGO risk score of 5–6. 4 Sita-Lumsden A Short D Lindsay I et al. Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000–2009. Br J Cancer. 2012; 107: 1810-1814 Crossref PubMed Scopus (88) Google Scholar Therefore, whether patients with a FIGO risk score of 5–6 should be treated with a multiagent approach, which is more aggressive than a single-agent approach, is controversial, 5 Winter MC Treatment of low-risk gestational trophoblastic neoplasia. Best Pract Res Clin Obstet Gynaecol. 2021; (published online Feb 2.)https://doi.org/10.1016/j.bpobgyn.2021.01.006 Crossref PubMed Scopus (1) Google Scholar , 6 Lok C van Trommel N Massuger L Golfier F Seckl M Clinical Working Party of the EOTTDPractical clinical guidelines of the EOTTD for treatment and referral of gestational trophoblastic disease. Eur J Cancer. 2020; 130: 228-240 Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar , 7 Braga A Mora P de Melo AC et al. Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide. World J Clin Oncol. 2019; 10: 28-37 Crossref PubMed Google Scholar even though most patients who do not respond to first-line single-agent chemotherapy can have complete remission after second-line single-agent chemotherapy. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort studyApproximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. Full-Text PDF

Folinic acid rescue during methotrexate treatment for low-risk gestational trophoblastic neoplasia – How much is just right?

ObjectiveTo compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with 8-day methotrexate (MTX) with two different regimens of folinic acid (FA). MethodsRetrospective cohort study of low-risk GTN followed at Rio de Janeiro Federal University, from January/2000-December/2019 with 8-day MTX with FA at 0.1 mg/kg versus 15 mg fixed dose. RESULTSAmong 667 patients with low-risk GTN, 323 were treated with FA at 0.1 mg/kg and 142 with FA at 15 mg fixed dose. The weight-based and fixed dose groups were comparable in terms of clinical profile but did differ in the hCG pretreatment level (8883 versus 5127 IU/L, p < 0.01) and FIGO risk score 5/6 (3.4% versus 18.3%, p < 0.01), respectively. Despite this, there was no difference in the remission rate in first-line treatment (76.8 versus 81%, p = 0.33), although FA at 0.1 mg/kg had a significantly higher number of chemotherapy cycles to remission (5 versus 4, p < 0.01), need to delay chemotherapy due to toxicity (6.8 versus 2.8%, p < 0.01) and time to remission, (12 versus 8 weeks, p < 0.01), respectively. A logistic regression analysis showed that the different FA rescue regimens appeared comparable in terms of achieving remission in first-line chemotherapy for low-risk GTN (OR:5.16, CI95%:0.84–31.64, p = 0.08). ConclusionFA with 15 mg fixed dose as compared to 0.1 mg/kg of FA was associated with similar primary remission rate, relapse or death among low-risk GTN treated with 8-day MTX. This regimen is highly practical, reduces visits to health facilities, appears equally safe and may be preferable with the 8-day MTX regimen in the treatment of low-risk GTN.

Comparison of weekly methotrexate regimen versus methotrexate folinic acid 8-day regimen for treatment of low-risk gestational trophoblastic neoplasia.

We aimed to compare weekly methotrexate (MTX) regimen and methotrexate-folinic acid (MTX-FA) 8-day regimen in the first line treatment of low-risk gestational trophoblastic neoplasia (GTN). The study included 73 patients with low-risk GTN according to FIGO risk score (FIGO risk score<7). All patients received either weekly MTX (30-50mg/m2 intramuscular weekly) or MTX-FA 8-day (MTX 1mg/kg IV on day 1, 3, 5, and 7, FA 15mg orally on day 2, 4, 6, and 8 given 24h after each MTX dose, every 14 days) regimens in the first-line treatment of low-risk GTN. The baseline clinicopathological characteristics and treatment outcomes were analyzed retrospectively. The median age of all patients was 29 (18-51) years, and the median FIGO risk score was 3 (1-6). Of the patients recruited, 53 received MTX-FA 8-day, and 20 had MTX weekly regimens. There was a significant difference between the two groups with respect to FIGO risk scores (3 [1-6] vs. 2 [1-5], p=0.023, MTX-FA 8-day vs. MTX weekly, respectively). The complete response rate was significantly higher in MTX-FA 8-day group compared to MTX weekly group (83% [44/53] vs. 60% [12/20] p=0.038). In univariate and multivariate regression analyses, only presence of lung metastasis was found to be an independent risk factor for treatment resistance (OR: 3.959, 95% CI 1.105-14.179, p=0.035). MTX-FA 8-day regimen is more effective than weekly MTX regimen in the first line treatment of low-risk GTN including patients even with higher FIGO risk scores. Treatment resistance may develop especially in patients with lung metastasis.

Histopathological examination of the curettage material in nonviable pregnancies and evaluation of the frequency of hydatidiform mole.

The study aimed to determine the frequency of possible missed diagnosis of gestational trophoblastic disease in nonviable pregnancies and to evaluate the importance of histopathological examination. In this retrospective study, the results of the histopathological assessment of patients undergoing uterine surgery with a diagnosis of nonviable pregnancy were analyzed before 14 weeks of gestation. Nonviable pregnancy was defined as anembryonic pregnancy and intrauterine exitus (IU-ex) based on ultrasound findings. The frequency and sonographic characteristics of molar pregnancy in nonviable pregnancy were analyzed. Molar pregnancy was detected in 24 (1.62%) of 1481 patients diagnosed with nonviable pregnancy on ultrasound. One thousand one hundred and twenty-one of the cases were IU-ex (75.69%) and the remaining were anembryonic pregnancy (24.31%). The mean crown-rump length of pregnancies in the IU-ex group was 16.7 mm and the mean gestational age was 8 weeks. The average gestational sac diameter was found to be 26 mm in anembryonic pregnancy patients. The hydatidiform mole ratio was significantly higher in anembryonic pregnancy patients (3.06%) than in IU-ex patients (1.16%) (p=0.013). The appearance of early molar pregnancy on ultrasound evaluation may mimic anembryonic pregnancies. Therefore, histopathological examination of anembryonic pregnancies may be useful in early diagnosis and for the treatment of gestational trophoblastic neoplasia.