Cases Of Gestational Trophoblastic Neoplasia Research Articles

Utility of manual vacuum aspiration followed by curettage in the treating hydatidiform mole: A retrospective analysis.

While manual vacuum aspiration (MVA) is commonly employed for early first-trimester abortions, its effectiveness in treating hydatidiform mole is still unclear. This study sought to evaluate the efficacy and safety of MVA in comparison to dilation and curettage (D&C) for managing hydatidiform mole. We conducted a retrospective review of medical records for 198 patients with hydatidiform mole treated at Nagoya University Hospital between 2004 and 2023. After excluding cases with incomplete data, we compared 106 patients who underwent D&C with 60 patients treated with MVA followed by curettage. We evaluated the surgical duration, intraoperative blood loss, and the occurrence of post-molar gestational trophoblastic neoplasia (GTN) in both groups. The surgical duration and blood loss were similar between the MVA and D&C groups. The average surgical time was 13.2 min for D&C and 11.8 min for MVA (p = 0.145). Most cases in both groups experienced blood loss of less than 10 mL, with no significant difference (p = 0.066). Over a median follow-up period of 33.4 months, 25 cases developed post-molar GTN. All GTN cases originated from complete hydatidiform mole (25 of 132 cases, 18.9%), and none were from partial hydatidiform mole. Kaplan-Meier analysis, focusing only on patients with complete hydatidiform mole, indicated no significant difference in the time to onset of GTN between the D&C and MVA groups (p = 0.632). MVA followed by curettage is a viable approach for treating molar pregnancy.

Organ-preserving treatment of a patient with a trophoblastic tumor of the placental bed (clinical observation and literature review)

Placental site trophoblastic tumor (PSTT) is а rare form of gestational trophoblastic neoplasia (GTN), accounting 0,2 % of total cases of GTN. PSTTs occur in women of childbearing age and most of them have strong desire to preserve fertility. PSSTs are tumors with unpredictable biological behavior, high chemo-resistance and possibly fatal outcome in case of metastatic disease.Hysterectomy is the primary treatment of choice in early disease. We report a rare clinical case of fertility sparing treatment for PSTT.

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.

Gestational trophoblastic neoplasia with concurrent metastasis to the mother and child: a systematic literature review.

Gestational trophoblastic neoplasia (GTN) arising in the placenta and presenting as a metastatic disease concurrently in the mother and the baby is extremely rare. GTN poses a diagnostic dilemma to the treating clinicians. In the current review, an electronic search of Scopus, PubMed, Embase and other databases was conducted for case reports and case series of GTN co-existing or metastatic to both the mother and the baby, published to date. Globally, a total of twenty-two cases of GTN with metastasis to both the mother and baby was found. The previous history of histopathology confirmed molar pregnancy was present in 4/22 cases. The median time to diagnose GTN in the mother was six weeks post-partum. In the majority of cases, diagnosis of maternal disease was made after the infant presented with clinical manifestation. Overall survival was reported in 17/22 mothers up to varying latest follow-up and in 6/22 infants. A knowledge of the varied clinical presentation, eliciting a history of previous pregnancy loss/term pregnancy and serum beta human chorionic gonadotrophin (β-hCG) estimations were helpful for early diagnosis. The concurrent presence of GTN in the mother and baby is a rare entity and poses a diagnostic dilemma. Diagnosis in the mother often follows diagnosis in the baby after an infant presents with clinical manifestations. GTN is a highly chemo-sensitive tumour, but the main prognostic factors determining survival are the time to diagnosis following previous pregnancy and serum β-hCG levels.

The impact of the distance traveled between residence and gestational trophoblastic neoplasia reference center and clinical outcomes in Brazilian women

ObjectiveTo relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission. Study designRetrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017. ResultsEvaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20–4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05–1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93–10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07–6.93), relapse (RR:10.27; 95%CI:3.08–34.28) and death due to GTN (RR:3.62; 95%CI:1.51–8.67). ConclusionsThe distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support.

Association of ultrasound morphological features with serum β subunit human chorionic gonadotrophin and histopathology among sonologically diagnosed cases of gestational trophoblastic neoplasia in a tertiary hospital

BACKGROUND: Gestational trophoblastic neoplasia (GTN) presents as vascular mass of varying morphology on ultrasound and confirmed through quantitative serum β subunit human chorionic gonadotrophin (β-hCG). In regions with limited access to β-hCG, ultrasound plays a crucial role in the initial diagnosis for timely management. OBJECTIVES: This study aimed to investigate the associations between ultrasound vascular morphologic features, serum β-hCG levels, and histopathology in GTN cases. METHODOLOGY: A cross-sectional review was conducted on 113 cases with ultrasound impression of GTN over an 8-year period. The patient data were extracted from case records, and ultrasound images were categorized based on the distinct features. Associations with β-hCG levels and histopathology were analyzed using the Chi-square test and Mann–Whitney U-test. Statistical significance was set at P < 0.05. RESULTS: A significant association was observed between ultrasound category and serum β-hCG (P < 0.0001). The compact and diffuse types were more prevalent with β-hCG levels between 104 to <105 mIU/mL, while the lacunar type was common among patients with ≥105 mIU/mL. However, there was no significant association between ultrasound categories and mean β-hCG levels. Regarding histopathology, the lacunar type was more common in invasive moles, whereas the compact and diffuse types tended to be seen with choriocarcinoma, although these were not statistically significant (P = 0.182). CONCLUSIONS: Morphologic types of GTN by gray scale and Doppler ultrasound vary across the different levels of serum β-hCG and may suggest the histopathological diagnosis. This study provides valuable insights into the ultrasonographic characteristics of GTN, which can aid in its diagnosis and management.

Anti-PD-1 therapy plus chemotherapy versus anti-PD-1 therapy alone in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia: a multicenter, retrospective study.

Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p<0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P=0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p=0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p<0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p=0.729). Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy. The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084).

A profile of Gestational Trophoblastic Neoplasia in a tertiary hospital in Surabaya, Indonesia

HIGHLIGHTS This study aimed to identify the characteristics of Gestational Trophoblastic Neoplasia (GTN). GTN is chemosensitive, but without appropriate therapy and follow-up, GTN will develop into complications and fatalities. ABSTRACT Objective: Gestational Trophoblastic Neoplasia (GTN) is a pregnancy-related malignancy due to abnormal proliferation of trophoblastic tissue. This study aimed to identify the characteristics of patients with GTN to help diagnose cases of GTN earlier and provide better treatment. Materials and Methods: This was a descriptive retrospective study on medical records of patients with GTN in Dr. Soetomo General Academic Hospital Surabaya, Indonesia, during the period of January 2018 to December 2020 with a total sampling technique. There were 41 patients with GTN included as study subjects. Results: Forty-one cases of GTN met the inclusion criteria out of the fifty medical records collected. The majority of patients aged 21 – 30 years old (34%) and had parity status without data (42%). Regarding the clinical profile based on prognostic factors, the predominant patients (71%) also had no data about the time interval between the end of the last pregnancy and the first time diagnosed by GTN, Those with more than 100,000 mIU/ml of beta-hCG levels were 32%, and those without metastases were 41.5%. Most patients belonged to the low-risk group (49%) and received chemotherapy (71%) with the MTX LD regimen (69%). Conclusion: GTN occurred predominantly in reproductive women that belonged to the low-risk group. Furthermore, chemotherapy is one of the chosen therapy for those patients.

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.

Gestational Trophoblastic Disease in Malta

Background: Gestational trophoblastic disease (GTD) is a group of uncommon conditions associated with pregnancy and includes a spectrum of premalignant to malignant disorders. The aim of this study is to determine the local incidence of GTD and to analyses the management that is being offered to patients with GTD in Mater Dei Hospital. Methodology: All patients diagnosed with GTD from 1st January 2015 till 31st December 2020 were studied. The list of patients with GTD was obtained from the Pathology Department and data was collected from medical records, iSOFT and electronic discharge summaries. Results: In this 6-year study period, 83 cases of GTD were identified. 79.5% of patients had partial hydatidiform mole and 16.9% had complete mole. 3.6% were cases of gestational trophoblastic neoplasia. 55.4% of patients received medical treatment with vaginal misoprostol and 27.7% had immediately surgical management. Their follow-up was studied; 21.7% had 3 out-patients visits or less, 33.7% had between 4 to 6 visits and 19.3% had 7 to 15 outpatients visits. 7.2% had extra oncology out-patients visits. 40% of patients had a follow-up that lasted for 7 months or more. Conclusion: GTD in Mater Dei Hospital appears to be an uncommon disease, but the local incidence was noted to be as high as 1 per 319 living births. This study demonstrated that a large number of patients were medically treated and the follow-up received was noted to be inconsistent. The care of these patients can be highly optimized by the set-up of a small dedicated clinic

Molecular profiling of gestational trophoblastic neoplasia: Identifying therapeutic targets (167)

Objectives: The molecular characterization of gestational trophoblastic neoplasia (GTN), a rare disease, has been limited by the lack of tumor specimens. Despite the recent use of immunotherapy, women with recurrent or chemo-resistant diseases have limited treatment options. Our objective was to describe the molecular landscape of GTNs and identify potential therapeutic targets. Methods: A total of 30 GTN tumor samples were analyzed using next-generation sequencing (NGS) or whole-exome sequencing (WES) and immunohistochemistry (IHC). PD-L1 IHC used SP-142 (cut-off ≥1%). MSI was tested by fragment analysis, IHC, and NGS. TMB was measured by totaling somatic mutations per tumor (high ≥10 mutations per MB). Statistical significance was determined by Chi-square and p-values adjusted for multiple comparisons (q) to be < 0.05. Results: Thirty cases of GTN consisted of 15 choriocarcinomas, three complete moles, seven epithelioid trophoblastic tumors (ETT), and five placental site trophoblastic tumors (PSTT) were included in the study. The median age was 41.5 years (range 26-69), and the majority (56.7%) were primary tumors. PD-L1 IHC was positive in 28/29 (96.6%) of cases while nearly all cases were TMB low (15/16, 93.8%) and microsatellite stable (MSS) (17/17, 100%). TP53 mutations were the most common, occurring in 33.3% of choriocarcinoma cases. Homologous recombination repair (HRR) pathway alterations were identified in 13.3% of choriocarcinoma cases. RTK-RAS pathway was altered in 2/5 (40%) ETT cases and 1/14 (7.1%) choriocarcinoma cases (Table 1). Conclusions: Data is consistent with previously published literature demonstrating high PDL1 expression across GTN subtypes, strongly supporting a role for checkpoint blockade. Potential alternate targeted therapies for recurrent or chemoresistant GTN include Wee1, PARP, MEK inhibitors targeting TP53, HRR, and KRAS alterations. Objectives: The molecular characterization of gestational trophoblastic neoplasia (GTN), a rare disease, has been limited by the lack of tumor specimens. Despite the recent use of immunotherapy, women with recurrent or chemo-resistant diseases have limited treatment options. Our objective was to describe the molecular landscape of GTNs and identify potential therapeutic targets. Methods: A total of 30 GTN tumor samples were analyzed using next-generation sequencing (NGS) or whole-exome sequencing (WES) and immunohistochemistry (IHC). PD-L1 IHC used SP-142 (cut-off ≥1%). MSI was tested by fragment analysis, IHC, and NGS. TMB was measured by totaling somatic mutations per tumor (high ≥10 mutations per MB). Statistical significance was determined by Chi-square and p-values adjusted for multiple comparisons (q) to be < 0.05. Results: Thirty cases of GTN consisted of 15 choriocarcinomas, three complete moles, seven epithelioid trophoblastic tumors (ETT), and five placental site trophoblastic tumors (PSTT) were included in the study. The median age was 41.5 years (range 26-69), and the majority (56.7%) were primary tumors. PD-L1 IHC was positive in 28/29 (96.6%) of cases while nearly all cases were TMB low (15/16, 93.8%) and microsatellite stable (MSS) (17/17, 100%). TP53 mutations were the most common, occurring in 33.3% of choriocarcinoma cases. Homologous recombination repair (HRR) pathway alterations were identified in 13.3% of choriocarcinoma cases. RTK-RAS pathway was altered in 2/5 (40%) ETT cases and 1/14 (7.1%) choriocarcinoma cases (Table 1). Conclusions: Data is consistent with previously published literature demonstrating high PDL1 expression across GTN subtypes, strongly supporting a role for checkpoint blockade. Potential alternate targeted therapies for recurrent or chemoresistant GTN include Wee1, PARP, MEK inhibitors targeting TP53, HRR, and KRAS alterations.

Evaluation of Incidence, Risk Factors, Diagnosis and Management of Gestational Trophoblastic Neoplasia: A Retrospective Study

Introduction: Detection of any definite established pattern in aetiological factors can help identify high risk groups among vesicular mole patients, so that the development of Gestational Trophoblastic Neoplasia (GTN) can be anticipated to avoid delay in management of this disease with almost 100% cure rate. Aim: To determine the incidence of GTN, various factors associated with the condition, and any difference in risk factors between low risk and high risk disease and to evaluate the efficacy of the different treatment protocols used. Materials and Methods: A retrospective descriptive study done in the Department of Obstetrics and Gynaecology in a tertiary level hospital in South India which included 100 cases of GTN who were registered in the Gestational Trophoblastic Disease (GTD) clinic for a period of ten years from January 2002 to December 2011. Data analysis was done from January 2020 to August 2020 The hospital incidence of GTN and proportion of GTN among vesicular mole was calculated. The different sociodemographic factors, clinical features and hormonal profile of all cases of GTN were studied in detail. Results: The incidence of GTN was 0.76 per 1000 deliveries. The proportion of GTN among molar pregnancy was 10.7%. Uterine size greater than period of amenorrhoea, bilateral theca leutin cysts especially with size &gt;6 cm and pre-evacuation Human Chorionic Gonadotropin (hCG) &gt;100,000 mIU/mL was associated with development of GTN. GTN was found more in those with complete mole and that was around 71%. Around 81% had low risk GTN and 19% had high risk GTN. Major indication for starting chemotherapy was rising βhCG (72%). Presence of theca lutein cysts and uterine size greater than period of amenorrhoea were statistically significant risk factors for high risk GTN (p=0.022 and p&lt;0.001, respectively). Conclusion: Identification of risk factors helps in early recognition of GTN and improves the overall outcome. The choice of chemotherapy depends on risk categorisation based on International Federation of Gynaecology and Obstetrics (FIGO) scoring system. Single agent for low risk and combination chemotherapy for high risk group is often sufficient.

Epidemiologic study on gestational trophoblastic diseases in Japan.

This study aims to estimate the population-based incidence of gestational trophoblastic diseases (GTDs) and to identify the characteristics of gestational trophoblastic neoplasia (GTN) in Japan. The annual number of GTD and live births from 1974 to 2018 were used to estimate the incidence of GTD. The data of 1,574 GTN cases from 1999 to 2018 were analyzed to identify the characteristics of low-risk GTN, high-risk GTN, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). The incidence of hydatidiform mole was 2.02 per 1,000 live births on average which decreased from 1974 to 2008 and increased from 2009 to 2018. The incidence of low-risk GTN, high-risk GTN, PSTT, and ETT was 15.3, 3.5, 0.3, and 0.07 per 100,000 live births, respectively. The estimated incidence of post-molar GTN was 9.8% of molar patients. High-risk GTN was diagnosed more pathologically, had more various kinds of antecedent pregnancies, and had longer intervals after the antecedent pregnancy compared to low-risk GTN. Furthermore, 8.2% of high-risk GTN occurred after the subsequent non-molar pregnancy of hydatidiform mole. The cumulative percentage of developing high-risk GTN after hydatidiform mole reached 89.3% at the 60th month. The incidence of hydatidiform mole, low-risk GTN, high-risk GTN was 2.02 per 1,000 live births, 15.3 per 100,000 live births, and 3.5 per 100,000 live births, respectively. High-risk GTN was diagnosed more pathologically and later after the antecedent pregnancy than low-risk GTN. Following molar patients for five years is needed to improve the mortality of malignant GTN.

The current state of pathology and immunohistochemistry in gestational trophoblastic disease therapeutic management: A tertiary center experience

Gestational trophoblastic disease (GTD) is derived from the abnormal development of trophoblastic tissue and covers a broad range of benign and malignant disorders. The histological diagnosis of GTD continues to be a challenge, even among expert pathologists. The present study evaluates the roles of pathology and immunohistochemistry in GTD diagnostic and therapeutic approaches. A retrospective study was conducted in Filantropia Clinical Hospital, Bucharest, Romania, involving cases of GTD between 2010 and 2020. We reported 19 clinically diagnosed and histologically confirmed cases of GTD, 15 moles (complete and partial), along with 4 cases of gestational trophoblastic neoplasia (GTN). The mean age of the patients studied was 31.3±7.5 years. The percentage of cases diagnosed after the sonographic evaluation was 94.7%. The rate of progression of GTD to GTN was 5.2%. Seven patients with low-risk GTD (risk score six or less) were treated with first-line chemotherapy (CT), and two cases required second-line CT. Twelve patients with highrisk GTD (risk score seven or more) were treated with first-line CT (n = 4), first-line CT followed by second-line CT (n = 4), first-line CT with adjuvant surgery (n = 3), and first-line surgery (one case). No causal relationship has been established between the forms of gestational trophoblastic disease regarding hCG level, the rate of normalization of hCG, and the rate of progression to GTN. After chemotherapy for GTD, only 42.1% of patients who wanted a future pregnancy could conceive. Underutilized in the current practice (5.2%), the immunohistochemical markers for trophoblasts and DNA genotyping are particularly useful tools in the fast and accurate diagnosis and prognosis of GTD.

Next-generation genome sequencing of a matched normal-tumor pair from a patient with intractable gestational choriocarcinoma: A case report.

Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) originating from trophoblastic cells with abnormal proliferation. Although chemotherapy is effective for treating this cancer, when patients develop chemoresistance, personalized treatment, such as the use of drugs matching their genomes, is required. The present report describes a case of intractable gestational choriocarcinoma identified using a next-generation sequencing (NGS)-based tumor panel. A 51-year-old woman was diagnosed with gestational choriocarcinoma via pathological and short tandem repeat analyses. The patient did not achieve remission despite many regimens of chemotherapy, including high-dose therapy with autologous peripheral blood stem cell transplantation. To identify drugs tailored to this particular choriocarcinoma, NGS was performed on the tumor of the patient, and the tumor genome was compared with that of the patient's blood sample using the NCC Oncopanel System. Consequently, 245 single nucleotide variants (SNVs) with a mean SNV allele frequency of 63.1% were identified. This high frequency was because the genome of the gestational choriocarcinoma contained part of the genome of the partner. Therefore, our experience of the present intractable case of choriocarcinoma suggested that matched normal-tumor pair analysis is not appropriate for treatment decisions in GTN cases. When using an NGS-based tumor panel to assess choriocarcinoma, researchers must consider whether the genomic DNA of the patient and their partner are involved in the GTN.

High Incidence of Gestational Trophoblastic Disease in a Third-Level University-Hospital, Italy: A Retrospective Cohort Study.

Introductionto assess incidence, prognosis and obstetric outcome of patients treated for gestational trophoblastic disease GTD in a twenty-year period. Incidence, prognosis and obstetric outcome of gestational throphoblastic diseaseMethodsretrospective study.ResultsFifty-four cases of GTD: 46 (85.18%) cases of Hydatidiform mole (HM); 8 cases of Persistent Gestational Trophoblastic Neoplasia (GTN) (14.81%): 6/8 cases (75%) GTN not metastatic; 2/8 cases (25%) GTN metastatic. In both cases, the metastases occurred in the lungs. In 3 out of 8 GTN cases (37.5%) a histological picture of choriocarcinoma emerged. The incidence of GTD cases treated from 2000 to 2020 was 1.8 cases per 1000 deliveries and 1.3 cases per 1000 pregnancies. Of the 54 patients, 30 (55.56%) presented showed normal serum hCG levels without the need for chemotherapy. On the other hand, 24 patients (44.44%) developed a persistent trophoblastic disease and underwent adjuvant therapy. The negative prognostic factors that affected the risk of persistence of GTD were: serum hCG levels at diagnosis > 100,000 mUI/ml; characteristic “snow storm” finding at the ultrasound diagnosis; a slow regression of serum hCG levels during follow-up; the persistence of high serum hCG levels (especially if > 1000 mUI/ml one month after suction curettage) that was the main risk factor for resistance to first-line chemotherapy. There were 10 pregnancies in total following treatment. Patients’ survival in our study was 100%.DiscussionAlthough GTD is a rare disease, its incidence was 1.3 cases per 1,000 pregnancies in Sardinia, Italy, higher if compared with mean national and worldwide incidence.

Gestational trophoblastic disease in Switzerland: retrospective study of the impact of a regional reference centre.

The European Society of Medical Oncology (ESMO) recommends that countries should have reference centres to provide adequate diagnosis and treatment of gestational trophoblastic disease. A trophoblastic disease centre in the French-speaking part of Switzerland was inaugurated in 2009. The objectives of this study were to report the activity of the centre during the last 10 years and analyse gestational trophoblastic disease outcomes. This was a retrospective study with data collected from all cases of gestational trophoblastic disease referred to the centre from 2009 to 2018. All histological specimens as well as data for treatment and follow-up of gestational trophoblastic disease and neoplasia were reviewed. Clinical features, including age, prognostic score and International Federation of Gynecology and Obstetrics (FIGO) stages (in the case of gestational trophoblastic neoplasia), human chorionic gonadotropin (hCG) follow-up, treatment and outcome were reported. The centre registered 354 patients, and these patients presented 156 cases of partial hydatidiform moles, 163 cases of complete hydatidiform moles and 14 cases of gestational trophoblastic neoplasia. During follow-up, 35 gestational trophoblastic neoplasms were diagnosed after hCG persistence. After pathology review, the overall agreement rates between our centre and a participating provider hospital was 82%. Methotrexate was the first line of single-agent chemotherapy for most patients, with resistance rates of 23%. Multi-agent chemotherapy was used as first-line treatment for five patients. None of the patients followed up by the centre died from gestational trophoblastic disease. This study reflects the activity of the Swiss trophoblastic disease centre from the French-speaking part of Switzerland created in 2009, and its role as local and national reference centre, in terms of global health, for women with gestational trophoblastic disease.

The Curative Effect of a Second Curettage in Low-Risk Gestational Trophoblastic Neoplasia

Background: Gestational trophoblastic neoplasia (GTN), despite its widespread metastases, is a very common cancer in women that is curable. Although the GTN cases show a good response to chemotherapy, in an effort to reduce toxic drug exposure, the second curettage has been suggested for some patients. In the current study, we have aimed to compare the benefits of the second curettage in comparison with single-agent chemotherapy for low-risk GTN patients.&#x0D; &#x0D; Methods: This retrospective observational study was carried out on GTN patients admitted to the gynecology department of Imam Khomeini Hospital in Ahvaz. The demographic profile of all participants was extracted. Patients&amp;#39; hospitalization records were also extracted from the files. Patients with an endometrial thickness above 10 mm were treated with re-curettage. The &amp;beta; hCG clearance time was estimated by the Kaplan Meier plot. &#x0D; &#x0D; Results: In the present study, 148 patients with low-risk GTN stage 1 were studied. The time required for &amp;beta;-hCG clearance in patients undergoing re-curettage was significantly lower than the chemotherapy receiving group (7 months vs. 10 months, p &amp;lt;0.0001). More than 50% of patients treated by re- curettage without needing chemotherapy. Moreover, the other 50% cases needed chemotherapy the number of courses was significantly lower than those received single-agent chemotherapy alone (p &amp;lt;0.0001). The baseline &amp;beta;-hCG levels were significantly lower in those who did not need chemotherapy (p = 0.012). &amp;beta;-hCG resolution occurred more rapidly in patients undergoing re-curettage alone, while, those who received only chemotherapy had a longer duration for &amp;beta;-hCG clearance.&#x0D; &#x0D; Conclusion: In general, the findings of this study showed that re-curettage could be used effectively in the treatment of GTN following molar pregnancy. This treatment reduces or eliminates the need for chemotherapy. Our findings also showed that the initial level of &amp;beta;-hCG could be considered as a predictive factor in response to curettage.

Evaluation the Recurrence Risk of Gestational Trophoblastic Neoplasia (GTN) after Serum βhCG Normalization

Background: Although many GTN patients can be treated with chemotherapy, a small proportion of them will relapse after complete recovery. To the best of our knowledge, there is not any information in respect of relapsed GTN cases in our region. In the current study we have aimed to evaluation of the recurrence risk of gestational trophoblastic neoplasia (GTN) after serum &amp;beta;hCG normalization Methods: This descriptive-analytical study was carried out on registered hospital data of patients with confirmed GTN diagnosis following molar pregnancy who admitted to the gynecology ward of Imam Khomeini Hospital between 2011 and 2017. Patients with diagnosis of postmolar GTN, based on at least five bhcg measurements was included. Patients information including initial level of serum BhcG, time to Bhcg resolution, types of molar pregnancy, treatment protocols, need to recuretage relapse, and finally, the period time between bhcg resolution to relapse were evaluated. Results: In the present study, 239 patients with GTN (including 180 complete and 59 partial moles) were evaluated. The mean age of the patients was 28.8 years, ranging from 16 to 47 years. The mean &amp;beta;hCG concentration was 170,000 IU/ml (ranged 760 to 850,000). The mean time of &amp;beta;hCG resolution was 8.19 months in the range of 4 to 12 months. Recurrence was observed in 9 patients (3.7%). The mean period time between &amp;beta;hCG resolution to relapse was 20.94 months. The mean initial level of &amp;beta;hCG was significantly lower in patients with recurrence (p &amp;lt;0.0001). The highest recurrence rate was seen in those receiving multiple-drug chemotherapy. There was also a significant relationship between disease stage and recurrence rate. Conclusion: The findings of this study indicate that although the recurrence of GTN is relatively low, given the poor prognosis of these patients, continuous evaluation of bHCG levels for at least two years is essential to prevent disease progression.

Management and prognostic analysis of patients with gestational trophoblastic neoplasia (GTN) in FIGO stage IV and its special type

GTN is a group malignant diseases from placental trophoblastic cells. There are very few cases of GTN with FIGO (International Federation of Gynecology and Obstetrics) stage IV all over the world, and the special types (patients with metastatic lesions and with no evidence of GTN neither in genitalia nor in lungs) have rarely been reported. It is necessary to conduct large retrospective studies aimed at exploring the diagnosis, treatment and outcomes of this disease. In this retrospective study, 716 patients with GTN were treated at Zhejiang University School of Medicine Women’s Hospital between January 1999 and September 2019; 26 patients were diagnosed as stage IV GTN; Among the 26 stage IV GTN patients, 5 were defined as the special types. The 5-year OS rate of the total 26 FIGO stage IV GTN patients was 69.0%. There was no significant difference of survival rate between stage IV GTN and its special type. And no significant differences in blood type, antecedent pregnancy type, the interval from last known pregnancy, pretreatment serum HCG (human chorionic gonadotropin) level, maximum diameter of tumors, FIGO score, underwent surgery or not and pathological pattern by the outcomes. Age, number of tumor lesions, primary chemotherapy regimen was EMA-CO or EP-EMA protocol and chemoresponse affected the prognosis significantly. Only number of tumor lesions > 8 was independent prognostic factors associated with poorer OS.