Diagnosis Of Gestational Trophoblastic Neoplasia Research Articles

Comparative Investigation of Color Doppler Ultrasonography Parameters of the Uterine Artery in Patients with Post-molar GTN and Patients Recovered from Molar Pregnancy and its Role in Predicting the Probability of Occurrence

Objectives: Hydatiform mole can progress to gestational trophoblastic neoplasia (GTN), and we are looking for non-invasive methods to predict it. Old age, higher serum BHCG levels, and expression of genes, such as VEGF-EG, HIF-1α, and TGF-ß are known as predictive factors. We performed this study to evaluate the role of bilateral uterine artery doppler ultrasound in predicting postmolar- GTN. Methods: In this prospective cohort study, 42 patients with complete molar pregnancy were examined. Inclusion criteria confirmed molar pregnancy by histopathological examination. Exclusion criteria were patients more than 40 years old, patients with completed family childbearing planning, and diagnosis of GTN during the routine histopathological study. Before molar evacuation and four weeks later, bilateral uterine artery doppler sonography to determine the PI, RI, and PSV was performed. Serum BHCG levels were also measured before molar evacuation and weekly after evacuation until it exhibited spontaneous remission or developed GTN. Results: About 36 patients were cured, and six others developed post-molar GTN. The bilateral uterine artery doppler sonography between the two groups showed a lower UA RI in the post-molar-GTN group before evacuation (P=0.048). Data demonstrated significant increases in Right.UA.RI (P=0/008), Left.UA.PI (P=0/037), and Right.UA.PSV (P=0/024) in the spontaneous remission group during 28 days follow-up period. There were no significant differences in these parameters in the GTN group throughout the time of follow-up. Conclusion: It seems that Doppler ultrasound plays a role in predicting GTN following uterine evacuation. A lower resistance in the uterine artery before evacuation and the remaining uterine artery blood flow constant after evacuation is associated with the development of post-molar- GTN.

Choriocarcinoma presenting as late postpartum hemorrhage in a 21-year-old primipara

INTRODUCTION: Obstetrical hemorrhage remains to be one of the most common causes of maternal morbidity and mortality. Postpartum hemorrhage occurs after delivery and is usually secondary to uterine atony, genital tract lacerations, and retained placental fragments. CASE: A case of a 21-year old, primipara, presented with profuse vaginal bleeding and hemoptysis at 3 weeks' postpartum. A clinical diagnosis of gestational trophoblastic neoplasia was established after an elevated serum beta human chorionic gonadotropin was obtained and an intrauterine mass was seen on ultrasonography, including metastasis to the lungs and liver seen through imaging studies. DISCUSSION: Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin (EMACO) is the mainstay treatment for Stage IV disease. However, complications such as hemorrhage and tumor rupture are best managed surgically. Although rare, a diagnosis of choriocarcinoma should be considered in patients with persistent bleeding after a normal pregnancy to institute proper management and avoid associated complications of tumor progression.

Mola hidatiforme parcial: a propósito de un caso

Gestational trophoblastic disease (GTD) is made up of a set of uncommon pathologies associated with pregnancy, ranging from benign to malignant; It has been described as several unusual benign and malignant processes, derived from an abnormal proliferation of the trophoblast of the human placenta, this groups a set of benign lesions such as hydatidiform mole and gestational trophoblastic neoplasia. Hydatidiform mole is a rare obstetric pathology, consisting of an abnormal pregnancy characterized by hydropic degeneration of the chorionic villi and trophoblastic hyperplasia, with a clinical presentation that warrants proper use of available diagnostic tests, especially ultrasound and Doppler , early in pregnancy, to establish its timely diagnosis, which will favorably improve the prognosis; In addition to performing histology, molecular genetic studies would be key to help in the diagnostic pathway. Its treatment of choice is uterine evacuation and strict monitoring with human chorionic gonadotropin (hCG), specifically of β-hCG levels, essential for early diagnosis of gestational trophoblastic neoplasia. High-risk trophoblastic disease (TGD) is treated with multidrug chemotherapy, with or without adjuvant surgery to remove resistant foci of disease, or radiation therapy for brain metastases.

Importance of pathological review of gestational trophoblastic diseases: results of the Belgian Gestational Trophoblastic Diseases Registry

ObjectiveTo evaluate the added value of a centralized pathology review of the diagnoses of gestational trophoblastic diseases by expert pathologists and its potential impact on clinical management in a prospective...

Analysis of patient experiences with gestational trophoblastic neoplasia reported on Instagram social media

ObjectiveThis study aimed to explore patient-reported content on Instagram social media posts focused on gestational trophoblastic neoplasia (GTN). Study designA cross-sectional search of public Instagram posts containing the term #gestationaltrophoblasticneoplasia from 1/1/2019–12/31/2019 was performed. This study included only patient-centered posts written in the English language posts. Investigators collected data for timing relative to diagnosis, subject matter, content, and tone. We utilized a staged approach to analyzing social media post content through familiarization, identifying the thematic framework, indexing, summarizing, and interpreting data. Descriptive statistical analysis was performed. ResultsIn total, of 326 extracted posts from 1/1/2019–12/31/2019, 291 (89.3%) met the criteria for study inclusion. The majority of content was posted during chemotherapy (n = 142, 48.8%) or in the surveillance period (n = 121, 41.6%) after completion of treatment. Qualitative analysis identified ten major themes: cancer therapy and side effects (n = 142, 48.8%), pregnancy loss (n = 59, 20.3%), labs and imaging (n = 60, 20.6%), acknowledgement of a support person (n = 37, 12.7%), infertility (n = 32, 11.0%), hardships of parenting during cancer (n = 21, 7.2%), religion/spirituality (n = 18, 6.2%), diagnosis (n = 12, 4.1%) fear of recurrence (n = 10, 3.4%) and surgery (n = 7, 2.4%). Further, of the posts focused on chemotherapy side effects, approximately one-half (n = 38, 46.3%) discussed hair loss, and fatigue was reported in 25.6% (n = 21) of posts. ConclusionsIn this cross-sectional study of Instagram posts using the hashtag #gestationaltrophoblasticneoplasia, we identify that women with GTN use Instagram posts to share experiences unique to their cancer diagnosis, including chemotherapy side effects, including hair loss, infertility, labs and imaging, and the hardships of parenting during cancer. This analysis provides important information regarding patient values and experiences following a diagnosis of GTN.

Diagnosis and management of gestational trophoblastic disease: 2021 update.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histological type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score ≥7 and Stage IV) is treated with multiagent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent treatment‐resistant tumors.

Surveillance for gestational trophoblastic neoplasia following molar pregnancy: a cost-effectiveness analysis

Historically, published guidelines for care after molar pregnancy recommended monitoring human chorionic gonadotropin levels for the development of gestational trophoblastic neoplasia until normal and then for 6 months after the first normal human chorionic gonadotropin. However, there are little data underlying such recommendations, and recent evidence has demonstrated that gestational trophoblastic neoplasia diagnosis after human chorionic gonadotropin normalization is rare. We sought to estimate the cost-effectiveness of alternative strategies for surveillance for gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after complete and partial molar pregnancy. A Markov-based cost-effectiveness model, using monthly cycles and terminating after 36 months/cycles, was constructed to compare alternative strategies for asymptomatic human chorionic gonadotropin surveillance after the first normal (none; monthly testing for 1, 3, 6, and 12 months; or every 3-month testing for 3, 6, and 12 months) for both complete and partial molar pregnancy. The risk of reduced surveillance was modeled by increasing the probability of high-risk disease at diagnosis. Probabilities, costs, and utilities were estimated from peer-reviewed literature, with all cost data applicable to the United States and adjusted to 2020 US dollars. The primary outcome was cost per quality-adjusted life year ($/quality-adjusted life year) with a $100,000/quality-adjusted life year willingness-to-pay threshold. Under base-case assumptions, we found no further surveillance after the first normal human chorionic gonadotropin to be the dominant strategy from both the healthcare system and societal perspectives, for both complete and partial molar pregnancy. After complete mole, this strategy had the lowest average cost (healthcare system, $144 vs maximum $283; societal, $152 vs maximum $443) and highest effectiveness (2.711 vs minimum 2.682 quality-adjusted life years). This strategy led to a slightly higher rate of death from gestational trophoblastic neoplasia (0.013% vs minimum 0.009%), although with high costs per gestational trophoblastic neoplasia death avoided (range, $214,000 to >$4 million). Societal perspective costs of lost wages had a greater impact on frequent surveillance costs than rare gestational trophoblastic neoplasia treatment costs, and no further surveillance was more favorable from this perspective in otherwise identical analyses. No further surveillance remained dominant or preferred with incremental cost-effectiveness ratio of <$100,000 in all analyses for partial mole, and most sensitivity analyses for complete mole. Under the assumption of no disutility from surveillance, surveillance strategies were more effective (by quality-adjusted life year) than no further surveillance, and a single human chorionic gonadotropin test at 3 months was found to be cost-effective after complete mole with incremental cost-effectiveness ratio of $53,261 from the healthcare perspective, but not from the societal perspective (incremental cost-effectiveness ratio, $288,783). Largely owing to the rare incidence of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after molar pregnancy, prolonged surveillance is not cost-effective under most assumptions. It would be reasonable to reduce, and potentially eliminate, current recommendations for surveillance after human chorionic gonadotropin normalization after molar pregnancy, particularly among partial moles. With any reduction in surveillance, patients should be counseled on symptoms of gestational trophoblastic neoplasia and established in routine gynecologic care.

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

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

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.

Response to Chemotherapy in Patients with Gestational Trophoblastic Neoplasia in A Tertiary Hospital in Indonesia

Background: The incidence of gestational trophoblastic neoplasia (GTN) is high in Indonesia. Based on the FIGO prognostic score, GTN is classified into low-risk and high-risk categories. The high-risk group requires multidrug chemotherapy whereas the low-risk group requires single-drug chemotherapy. Response to chemotherapy would reflect the remission rate. The aim of this study was to describe the response to chemotherapy in GTN patients Methods: This was a cross-sectional descriptive retrospective study on medical records of patients with GTN treated in Dr. Hasan Sadikin General Hospital during the period of 2016 to 2018. The inclusion criteria were GTN patients who received &gt; 3 cycles of chemotherapy while the exclusion criteria were incomplete, inaccessible, or missing data. Data were collected on patient’s age, parity, history of previous pregnancy, pregnancy-therapy interval, tumor size, number and location of metastases, and history of failed chemotherapy. Results: Of the189 medical records of the GTN patient collected, only 88 met the inclusion criteria, (63.6% low risk and 36.4% high risk). Most patients were responsive to chemotherapy (61.4%), aged&lt;40 years old, multiparity, tumor size &gt;5 cm, had 4 month interval from previous pregnancy &lt;4 months, had a history of molar pregnancy, had no metastases, and no previous failed chemotherapy. Conclusion: The chemotherapy response in gestational trophoblastic neoplasm patients is fairly good with most patients are in the low-risk groups. Specific tumor markers used in early diagnosis of GTN may play a major role.

Post-Molar Stage I Low-Risk Gestational Trophoblastic Neoplasia: Transvaginal Ultrasound Findings and Their Correlation with Chemotherapy Response

Background: Early diagnosis of gestational trophoblastic neoplasia and its complications are pivotal for prompt and efficacious treatment. Transvaginal pelvic ultrasound could detect myometrial invasion and endometrial thickening following dilation and evacuation of hydatiform mole and also in the assessment of response to chemotherapy. Objectives: In this study we aimed to investigate transvaginal ultrasound findings of stage I low-risk gestational trophoblastic neoplasia (GTN) and whether there is an association between ultrasound findings and chemotherapy response. Patients and Methods: This study included 31 consecutive patients with postmolar stage I low-risk GTN. We recorded International Federation of Gynecology and Obstetrics (FIGO) score, and transvaginal ultrasound findings including color and pulsed Doppler interrogation at the time of beta human chorionic gonadotropin (β-hCG) rise. The number of Act-D cycles that each patient needed to achieve complete remission was also recorded. Results: Of the 31 patients with post-evacuation trans-vaginal ultrasound evaluation, 2 (6.5%) patients had no detectable finding, 4 (12.9%) had lesions limited to the endometrium, 12 (38.7%) had lesions with 50% invasion into myometrium, 4 (12.9%) had lesions that reached uterine serosal surface and 2 (6.5%) had arteriovenous malformation (AVM)-like myometrial lesions. The number of Act-D cycles patients needed to achieve remission was 6 cycles in patients with no finding, lesion limited to endometrium and less than 50% myometrial invasion and was 8 cycles in patients with > 50% invasion ± involvement of serosal surface. One patient in first group and two in second group need multi-agent chemotherapy. But these differences were not significant (P = 0.172). Conclusion: There was a non-significant increase in treatment duration and need of multiagent chemotherapy with more extensive ultrasound findings among patients with stage I low risk GTN.

A review on management of gestational trophoblastic neoplasia.

Background:The rare presence of malignant cancerous cells afar any type of pregnancy is known as gestational trophoblastic neoplasia (GTN). GTN are benign lesions which mostly happen due to the activity of extravillous trophoblast cells and the placental villous tree development. These kinds of diseases would be occurring mainly due to the following clinicopathologic conditions: (I) existence of epithelioid trophoblastic tumor (ETT), (II) rare type of choriocarcinoma cancer, (III) gestational trophoblastic tumor of mole, and (IV) the rare malignant tumor of placental site trophoblastic tumor.Objective:This comprehensive study is trying to review the most recent approaches in comprehension of pathogenesis, more precise diagnosis, and also the most effective therapeutic procedures for patients who suffer from GTN disorders.Materials and Method:A comprehensive research was carried out on scientific databases of Science Citation Index (SCI), MEDLINE, EMBASE, HMIC, PubMed, CINAHL, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), and PsycINFO over the time period of 2005 to 2019. The keywords which applied for discovering more related records were including: Gestational trophoblastic diseases (GTD), Gestational trophoblastic neoplasia (GTN), molar pregnancy, choriocarcinoma, human chorionic gonadotropin (hCG), diagnosis, management and treatment.Conclusion:In spite of the fact that GTN patients are treated with conventional surgical therapies or/and chemotherapy, in some patients with resistant disease, these therapies may not be effective and patients may die. Some novel remedial agents are required for decreasing the level of toxicity caused through administering conventional chemotherapy and also treating the patients who suffer from refractory or resistant disease. The newest issues are related to GTN diagnosis, process of progression of hydatidiform mole (HM) to GTN, and the issue of GTN drug resistance. In this regard, we should have a comprehensive knowledge on GTN genetics for answering all the available questions about this disorder.

1279 Total Laparoscopic Hysterectomy in an 18 Week Sized Uterus with Persistent Gestational Trophoblastic Disease

Video Objective To describe and illustrate an innovative minimally invasive surgical technique to allow a total laparoscopic hysterectomy with safe and feasible extraction of an 18 week sized uterus with gestational trophoblastic neoplasia (GTN). Setting The patient is a 44 year old G4P2012 with a diagnosis of GTN, status post dilation and evacuation with increasing b-hCG levels during follow-up. Workup for metastatic disease was negative. She completed childbearing and opted for a hysterectomy as definitive treatment. Interventions Intraoperatively, the uterus appeared to be 18 weeks in size. Laparoscopic dissection started by bilateral salpingectomy and transection of the utero-ovarian ligaments, preserving the ovaries. The broad ligament was then skeletonized, and the round ligaments were transected bilaterally. The bladder flap was created, and the uterine vessels were transected bilaterally using an advanced bipolar device. A sponge on a stick soaked in methylene blue was used to delineate the cervix and vagina. The cervix was then dilated to 14’’ and evacuation was performed using 12 suction. The suction continued until all products were removed and the uterus was significantly smaller in size. The colpotomy was performed and the uterus was extracted intact. Conclusion This is the first case in the literature to describe a minimally invasive technique that demonstrates a safe and feasible laparoscopic removal of an enlarged uterus and illustrates alternative extraction techniques to avoid laparotomy in GTN. In this case, a combination of laparoscopic transection of vascular pedicles followed by a dilation and evacuation was used prior to colpotomy. The addition of dilation and evacuation allowed us to reduce the overall size of the uterus and remove it intact through the vagina with minimal bleeding, avoiding unnecessary laparotomy. This allowed the patient to have a faster post-surgical recovery, minimal blood loss (EBL 20) and no hospitalization in comparison to standard laparotomy for persistent GTN.

GestaTIonal TrophoblAstic NeoplasIa Ultrasound assessMent: TITANIUM study

BackgroundThere are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients...

Is Not It the Time to Change the Treatment of Intermediate-Risk Patients Suffering From Gestational Trophoblastic Neoplasia?

Objectives: The present study attempted to provide a clear view of gestational trophoblastic neoplasia (GTN) with the focus on resistance to treatment approaches in Iran. Materials and Methods: This retrospective cohort study reviewed the medical records of 272 patients with the definitive diagnosis of GTN referring to Imam Khomeini hospital in Tehran during 2007-2017. Results: The mean age of participants was 29.19 ± 7.46 years. The abnormal uterine bleeding (AUB) was the most common clinical manifestation in 64.3% of patients. Regarding the risk scoring condition according to the World Health Organization criteria, 77.6%, 9.1%, and 13.3% were categorized as low-, intermediate-, and high-risk cases. Single therapy with methotrexate was used in 22.8% of patients and actinomycin-D was planned for 42.3% whereas 11.0% and 1.5% were considered for treatment with the EMA-CO (Etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) and EMA-EP (Etoposide methotrexate and actinomycin-D/ etoposide and cisplatin) regimens, respectively. Good response to methotrexate was 66.7% but it was 83.6% in the ACT group (P = 0.001). The resistance to single-agent chemotherapy in low- and intermediate-risk groups was 16% and 92%, respectively. In addition, 20.2% of patients in stage one had tumor invasion pattern in the uterus in pretreatment Doppler ultrasonography, but 52% and 30% had resistance to chemotherapy treatment in invasive and noninvasive groups, respectively (P = 0.008). Conclusions: In general, due to the high resistance of the intermediate-risk subgroup to a single therapy, a combination therapy may be more useful to treat this disorder. The close association between tumor invasion pattern in the uterus in Doppler ultrasonography and drug resistance can be considered as a new criterion for tumor risk scoring.

Update on the diagnosis and management of gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecologyand Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes.Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normallyor not normally distributed. Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P= .03), but there was no differencein recurrence (13% vs 11%, P= .89). Patients with high-risk gestational trophoblastic neoplasia lived 63miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long-distance travelers had a longer period between antecedentpregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P= .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P=.03). In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long-distance travelers.

Persistently raised and falling hCG at 6 months no longer a criterion for post molar gestational trophoblastic neoplasia?

Taylor et al. address an interesting question: Is simple observation without chemotherapy safe in cases of persistent positive and declining hCG levels 6 months after evacuation of a molar pregnancy? Considering the current FIGO criterion for post molar GTN diagnosis (persistently raised hCG concentration at 6 months), this question is important in avoiding unnecessary toxic chemotherapy treatment. Using the Sheffield and London databases of more than 16 000 molar pregnancies in 10 years, the authors identified 35 eligible women with raised but falling hCG 6 months after evacuation of a molar pregnancy. HCG levels fell spontaneously to normal levels without chemotherapy in 86% of patients and only 11% of patients (n = 4) were treated with single agent chemotherapy. Disease-free and overall survivals were 100%, demonstrating a safe ‘wait and see’ policy. However, the design and the results of the study raise some questions. First, some of the patients included in this study have already been included in a previous similar retrospective study from Agarwal et al. In the latter study, 66 patients from Charing Cross had been included over 15 years, whereas in the present study, only 18 patients from Charing Cross were identified in 10 years. This raises questions about such an unexpected decrease in incidence of persistently raised hCG levels at 6 months at Charing Cross. Secondly, one wonders whether the four patients treated with chemotherapy were accurately classified as a GTN as defined by FIGO (rise of hCG on at least three consecutive weekly measurements or plateauing of hCG concentrations during four weekly measurements). It is likely that if these criteria had been respected, chemotherapy might have been avoided in some of these patients, bringing the success rate of the observation strategy closer to the 98% rate reported 2 years ago by Agarwal et al. Thirdly, the observation that two patients did not respond to methotrexate (MTX) and returned to normal after dactinomycin does not necessarily mean that this second line treatment was curative. It has already been shown that stopping inefficient MTX chemotherapy may be associated with hCG returning to normal or with persistently low levels of hCG of undetermined significance in otherwise healthy women. Without taking into account these biases and weaknesses inherent in its retrospective design, this study should be considered to confirm previous data showing that the diagnosis of post molar gestational trophoblastic neoplasia (GTN) is no longer relevant in all women with persistently raised and falling hCG 6 months after evacuation of a molar pregnancy. The confusing terminology of persistent molar pregnancy should be abandoned until we understand why spontaneous hCG regression is so variable after molar pregnancies, ranging from less than 8 weeks to up to 2 years. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia

Circulating Tumor DNA: A Potential Novel Diagnostic Approach in Gestational Trophoblastic Neoplasia

Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling.

BackgroundIn randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes.MethodsA model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles.ResultsThe resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes.ConclusionThe use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-015-0106-y) contains supplementary material, which is available to authorized users.