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Gestational trophoblastic neoplasia (GTN) with spinal metastasis is rare with few documented cases worldwide. Few studies have explored chemotherapy combined with radiotherapy in the treatment of such cases. However, because of its rarity, there is still no standardized treatment regimen. A 34‐year‐old Gravida 1 Para 0 (0010) was diagnosed with GTN with metastasis to the lumbosacral spine, resulting in conus medullaris syndrome with lumbar radiculopathy. She presented with a 14‐month history of amenorrhea, left lower extremity pain, and urinary and bowel retention. On examination, there was a 10.0 × 7.0 cm lumbosacral mass and atrophy of the left lower extremity. Transvaginal ultrasound showed a cul de sac mass, and diluted β‐human chorionic gonadotropin (β‐hCG) titer was markedly elevated at more than 1000 000 mIU/mL. Magnetic resonance imaging (MRI) of the lumbosacral spine showed an ill‐defined sacral mass measuring 13.3 × 11.5 × 6.3 cm with spinal canal, bone, muscle, and nerve root involvement. She was treated with 10 cycles of EMACO and palliative radiotherapy with 10 sessions of 30 Gy of external beam radiation therapy directed toward the lumbosacral mass. Repeat MRI showed a decrease in size of the mass to 6.6 × 8.2 × 4.1 cm with concurrent decrease in β‐hCG to 1.30 mIU/ml, and resolution of leg pain and urinary and bowel symptoms. She was declared to be in remission 3 months after the last cycle of EMACO. [ABSTRACT FROM AUTHOR]

Choriocarcinoma can be gestational and nongestational. Gestational choriocarcinoma is rare with an incidence of 9.2 in 40,000 pregnancies in Asian population. They can occur following molar, partial molar pregnancy, abortion, or delivery. It is detected by elevated levels of serum beta-human chorionic gonadotropin (beta-hCG) and by imaging modality. The need for histopathological diagnosis for choriocarcinoma is debatable. Six cases of choriocarcinoma are described with variable presentations and outcomes. Out of six cases, three were following vaginal delivery, two were after abortion, and one case was perimenopausal with antecedent pregnancy 10 years ago, unclear whether it was the cause for choriocarcinoma. Brain and lung metastasis were seen in three cases each; one case, which had metastasis to all organs, had worse prognosis and succumbed to the disease. All belonged to high-risk group according to International Federation of Gynaecology and Obstetrics score (8–13). The prognosis is usually very good, provided that prompt diagnosis and treatment are initiated early. Long-term follow-up with beta-hCG levels needs to be done to detect recurrence but it did not act like a prognostic indicator in our case series. [ABSTRACT FROM AUTHOR]

Determine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). A cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. Mean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. Compared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN. • Single agent chemotherapy for low-risk GTN has higher costs and higher effectiveness compared to hysterectomy. • There is an additional cost of $74,526 CAD ($54,516 USD) for each additional QALY achieved with chemotherapy. • Single agent chemotherapy cost, risk of resistance, and chemotherapy duration are key factors impacting treatment costs. [ABSTRACT FROM AUTHOR]

Opinion Statement: In addressing Gestational Trophoblastic Neoplasia (GTN), it is imperative to acknowledge the evolving landscape of treatment options, especially in light of the challenges posed by traditional methods. While historically, surgical interventions, radiation therapy, and chemotherapeutic agents have been the mainstays, the emergence of resistance and high-risk scenarios necessitates a reevaluation of our therapeutic approaches. Our review highlights the promising advancements in immunotherapy and molecular targeted therapy as viable alternatives for GTN management. The introduction of immune checkpoint inhibitors and kinase inhibitors offers a paradigm shift, particularly for patients resistant to conventional chemotherapy regimens. These novel therapies not only exhibit efficacy but also demonstrate manageable toxicity profiles, particularly in high-risk cases. However, integrating these innovative treatments into established international guidelines presents a formidable task. As we move forward, it is imperative that future research not only prioritizes fertility preservation but also rigorously evaluates long-term toxicity implications. International collaboration becomes pivotal in addressing the nuances of this rare and complex disease. In conclusion, our review underscores the need for a nuanced approach to GTN treatment, one that prioritizes reduced toxicity and improved quality of life. By embracing the advancements in immunotherapy and molecular targeted therapy, we can pave the way for more effective and patient-centered care in the management of GTN. [ABSTRACT FROM AUTHOR]

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Introduction: Gestational trophoblastic neoplasia (GTN) is a malignant form of gestational trophoblastic diseases originating from abnormal proliferation of placental trophoblasts. Owing to unusual and variable presentations, the diagnosis is sometimes delayed and become catastrophic. Though, survival outcomes are good following chemotherapy, but still surgery becomes first choice in hemodynamically unstable patient which is to be followed by chemotherapy depending upon the World Health Organization (WHO) prognostic score. The reproductive outcomes following chemotherapy is variable. Here, we are reporting a case series of GTN with varied presentation giving different lessons which were managed to best of our possible efforts. Case discussion: The first case highlights the management of women who had ruptured choriocarcinoma post manual vaginal examination for which hysterectomy was performed as a life-saving procedure followed by chemotherapy. The other case surprised the clinician with metastatic perforating invasive mole along with unusual finding of ovarian and iliac vein thrombosis. Although, planned for chemotherapy, hysterectomy with debulking was done for hemoperitoneum. The last case perplexed us with the normal twin conception just following the completion of chemotherapy for post-molar high-risk GTN and is continuing her viable pregnancy. Conclusion and clinical implication: Our case series imparted few lessons to obstetricians. Pelvic examination in GTN needs to be guarded so as to prevent untoward life-threatening complications. Invasive mole may present lately with devastating rupture uterus with exuberant pelvic vein thrombosis (PVT). Spontaneous conception with good reproductive outcome may still occur immediately following completion of multi-agent chemotherapy in high-risk GTN. [ABSTRACT FROM AUTHOR]

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Gestational trophoblastic neoplasia (GTN) is extremely rare, but has a very good prognosis, with a cure rate close to 100%, for low-risk diseases. This article describes the case of a healthy 28-year-old nulliparous patient with GTN resistant to multiple lines of treatment. The era of immunotherapy is revolutionizing oncology, having already proved its worth in the treatment of many cancers. This article will have a specific focus on the emerging role of immunotherapy in the treatment of GTN. Unfortunately, the use of an immune checkpoint inhibitor (ICI) failed in our case, emphasizing on the necessity to clearly define the future role of immune therapy in GTN. Finally, given the rapid progression of the disease after hysterectomy, induction with Paclitaxel- Ifosfamide and then intensification with high-dose Carboplatin and Etoposide with peripheral blood stem cell support was given as a rescue therapy with still curative intent. [ABSTRACT FROM AUTHOR]

Backgrounds: Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results: Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of "fear and worry about choriocarcinoma recurrence". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions: IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration: N/A. [ABSTRACT FROM AUTHOR]

The treatment for high risk or recurrent gestational trophoblastic neoplasia (GTN) is a highly toxic multi-agent chemotherapy. For patients with progressive or recurrent GTN, checkpoint inhibitors have demonstrated anti-tumor activity; however, identification of novel therapies for GTN remain an unmet need. Therefore, we sought to characterize the molecular landscape of GTN to identify potential therapeutic targets. GTN samples were analyzed using a combination of molecular – next-generation sequencing (NGS) or whole exome sequencing (WES)- and protein- Immunohistochemistry (IHC) analyses. GTN samples encompassed complete moles, choriocarcinoma, epithelioid trophoblastic tumors (ETT), and placental site trophoblastic tumors (PSTT). We analyzed 30 cases of GTN including 15 choriocarcinoma, 7 ETT, 5 PSTT, 1 invasive mole and 2 mixed histologies. The median age was 41.5. GTN samples were found to be PD-L1 positive (92.3%), tumor mutational burden (TMB) low (92.8%), and microsatellite stable (MSS) (100%). Forty-six percent of choriocarcinoma specimens contained a genomic alteration including TP53 (33%) and homologous recombination repair (HRR) (13%) genes. Alterations in RTK-RAS pathway signaling was present in 40% of ETT cases. The high rate of PD-L1 positivity in this real-world database and reported in prior literature support continued clinical trial development evaluating immunotherapy for treatment of GTN. Other potential targeted treatments identified include Wee1, PARP and MEK inhibitors based on molecular alterations in TP53 , HRR genes, and RTK-RAS pathways respectively. • Treatment for recurrent GTN often requires multi-agent chemotherapy with high levels of toxicity. • Understanding the molecular profile of GTN may help identify less toxic, targeted therapies. • GTN samples express PD-L1 > 90% of the time. • ETT samples had alterations in the RTK-RAS pathway >40% of the time. [ABSTRACT FROM AUTHOR]

Background: Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD. Objectives: The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery. Methods: Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952–2022. Articles written in English, Spanish, and French were included. Outcomes: Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental. Conclusion and Outlook: Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps. [ABSTRACT FROM AUTHOR]

Background: Epithelioid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are two of the rarest GTNs that share certain features at diagnosis and management. Atypical Placental Site Nodule (APSN) is a relatively new entity considered as a premalignant lesion. Objectives and Methods: The aim of this review was to summarize the main characteristics of each of these entities, their diagnostic features, and their treatment's standard of care including fertility-sparing treatments. Outcome: This study provides a thorough review of ETT, PSTT, and APSN. Conclusions: The reader will gain an insight view of these rare tumors arising from the intermediate trophoblast. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint immunotherapy (CPI) targeting programmed cell death 1 (PD-1)/ligand (PD-L1) has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high-risk disease, and epithelioid trophoblastic tumour/placental site trophoblastic tumour subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease. Objectives: We set out to generate an overview of the current data supporting the use of CPI for GTN in both high-risk and low-risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines. Methods: We identified and reviewed the published data on the use of CPI agents in GTN. Outcome: 133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15), or other anti-PD-1 agents (16), of whom 118 had high-risk diseases, relapse or multi-drug resistant disease, and 15 low-risk diseases. Overall 85 patients achieved complete remission, 77 (of 118) with high-risk disease, and 8 (of 15) with low-risk disease. 1 patient with complete remission in the high-risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies. Conclusions and Outlook: The majority of high-risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes in gestational trophoblastic disease (GTD) are generally excellent, but GTD is a rare and complex condition that requires specialist information and support to offer a gold standard of care. Across Europe, specialist nurses and/or midwives are increasingly common in the GTD multidisciplinary team to work alongside medical professionals in a holistic model of care; however, the role is sometimes non-existent or can vary significantly between GTD centres. Objectives: The aim of the European Organisation for Treatment of Trophoblastic Diseases' (EOTTD) is to harmonise best practice in Europe. To provide a basis for the European standardisation of best practice nursing care in GTD, a group of European GTD nurses/midwives composed guidelines for minimal requirements and optimal nursing care of GTD patients. Methods: Members of the EOTTD member countries with nursing representation attended multiple workshops, both virtual and in person, and guidelines were created by consensus and evidence where available. Outcome: 16 nurses and 1 midwife from 4 countries (England, Ireland, Sweden, and the Netherlands) contributed. The group created flow diagrams for treatment and screening patients, showing minimum and best practice nursing care for patients with GTD. Conclusion: Despite the many different models of care and resources available to GTD services, this consensus working group has provided a set of guidelines to drive forward a patient focused holistic model of care for GTD patients. This is an original paper, whereby no such guidelines in GTD nursing have been developed before. The implementation of guidelines will encourage other health care professionals to improve the provision of patient care. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In young women presenting with atypical features of intracerebral hemorrhage, metastatic choriocarcinoma should be considered as a differential diagnosis. In resource‐poor settings, a high index of suspicion and serum β‐hCG are crucial for diagnosis. Intracerebral hemorrhage in the young is rarely caused by metastatic choriocarcinoma. Diagnosis of this condition may be particularly challenging in resource‐poor settings where access to diagnostic technologies may be limited. We present a case series of three young females diagnosed with metastatic choriocarcinoma after initially presenting with intracerebral hemorrhage, each demonstrating unique clinical manifestations. We aim to highlight the diagnostic considerations in the management of this infrequently encountered cause of intracerebral hemorrhage, especially in resource‐constrained settings. Case 1 involved a 21‐year‐old woman who was initially diagnosed with intracerebral hemorrhage likely of tumoral origin from an unknown primary source. Further evaluation revealed extremely high levels of β‐hCG and features suggestive of an intrauterine malignancy, which led to a diagnosis of metastatic choriocarcinoma. This further became complicated by pulmonary embolism. Unfortunately, she succumbed to respiratory failure during treatment. Case 2 is a young woman who presented to the emergency unit and was managed as a case of lobar intracerebral hemorrhage. Further checks revealed a previous history of hysterectomy done on account of placental site trophoblastic tumor, which promoted an evaluation for choriocarcinoma. Case 3 involved a 20‐year‐old patient who initially presented with headache and vomiting. An enhanced magnetic resonance imaging showed a large subacute right temporal occipital subependymal hemorrhage with mass effect. After probing further, we discovered that she underwent exploratory laparotomy for suspected ruptured ectopic gestation, which later turned out to be a gestational trophoblastic neoplasia. After further evaluation a diagnosis of choriocarcinoma with brain metastasis. Our case series emphasizes the importance of having a high index suspicion in young females who present with atypical features of ICH. The varied clinical scenarios highlight the challenges in diagnosing young females. It also underscores the critical role of serum β$$ \beta $$‐hCG, especially in resource‐limited settings where biopsies are not readily available. Building a repository of these diverse manifestations is essential for increasing the index of suspicion and ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose The aim of this review is to provide an overview of existing literature and current knowledge on fertility rates and reproductive outcomes after gestational trophoblastic disease. Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders associated with abnormal proliferation of trophoblast and their course is characterized by varying degrees of malignancy. WHO classified GTD into three categories: tumor-like lesions, molar pregnancies and gestational trophoblastic neoplasms. HM is characterized by abnormal proliferation of both syncytiotrophoblast and cytotrophoblast, edema of placental villi, with or without the presence of a fetus. Complete and partial moles have been classified as two separate disease entities, and their division depends on the genetic material they contain. The complete mole has a complete set of chromosomes coming only from the paternal genome, while the partial mole is triploid and the genetic material transferred comes from the father and mother. Post-molar gestational trophoblast neoplasia (GTN) is a clinical diagnosis based on the observation of a persistent increase or persistently high hCG concentration after evacuation of the mole, requiring evaluation and treatment. Invasive hydatidiform mole, together with choriocarcinoma and placental tumor, belong to gestational trophoblast neoplasia. Currently, research has shown that short tandem repeat (STR) genotyping is the gold standard for making the correct diagnosis and this test should be performed if possible. Ultrasound examination has replaced all other non-invasive methods of diagnosing gestational trophoblastic disease. Imaging tests can show: an empty fetal egg, a "blizzard" image, and fetal death around the 8th-10th week of pregnancy. After the end of a mole pregnancy, patients must have the hCG (chorionic gonadotropin) level in the blood serum checked on days 1, 7, 14, 21, etc. To talk about a favorable prognosis after the treatment is to achieve normal hCG level within 18 weeks. It is also extremely important to determine the stage of advancement of cancer lesions in order to implement appropriate treatment. To determine the invasiveness of GTN several laboratory and imaging tests must be performed which will enable us to determine cancer progression with the greatest possible accuracy. GTD diseases originate from both syncytiotrophoblast and cytotrophoblast tissues and as a result of which they produce an extremely sensitive marker - human chorionic gonadotropin. The facts stated above and significant sensitivity to chemotherapy mean that the average cure rate for this disease currently exceeds 90%. Although the main treatment of gestational trophoblast neoplasia involves the use of cytostatics, in cases with worse prognosis, i.e. those with a higher risk, surgery turns out to be an invaluable treatment method. [ABSTRACT FROM AUTHOR]

PurposeCurrently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN.MethodsThis retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (≥467.02) and a low PNI (≤51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI.ResultsNinety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapy-resistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P

المخلص: أهداف البحث: لدى مستقبلات فيتامين د أدوار كمضاد للسرطان لأنواع مختلفة من السرطانات. الهدف من هذه الدراسة هو تحديد الفروق في مستويات مستقبلات فيتامين د بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي. طرق البحث: هذه دراسة مقارنة شملت ستة وستين نسيجا تم جمعها من الورم الحويصلي المائي وورم النسيج الترويفي الحملي. تم إجراء اختبار ''تي'' واختبار ''مان ويتني'' لمقارنة التعبير المناعي لمستقبلات فيتامين د، بما في ذلك شدة مستقبلات فيتامين د، توزيع مستقبلات فيتامين د، والتقدير التاريخي بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي. النتائج: تم تضمين ما مجموعه ستة وستين عينة من الأنسجة في هذه الدراسة، تتألف من سبعة وثلاثين نسيجا تم تشخيصها بالورم الحويصلي المائي وأربعة وعشرين نسيجا تم تشخيصها بورم النسيج الترويفي الحملي. تمت المقارنة بين العمر والأعداد بين المرضى الذين يعانون من الورم الحويصلي المائي والمرضى الذين يعانون من ورم النسيج الترويفي الحملي، ولم يلاحظ وجود فروقات كبيرة في كلا المجموعتين. بالنسبة لحالات ورم النسيج الترويفي الحملي، كانت شدة مستقبلات فيتامين د أقل بشكل ملحوظ من شدة مستقبلات فيتامين د في نسيج الورم الحويصلي المائي. بالإضافة إلى ذلك، كان التقدير التاريخي في نسيج ورم النسيج الترويفي الحملي أقل بشكل ملحوظ من التقدير التاريخي في نسيج الورم الحويصلي المائي. ومع ذلك، لم يكن هناك فروقات كبيرة في توزيع مستقبلات فيتامين د بين نسيج ورم النسيج الترويفي الحملي ونسيج الورم الحويصلي المائي. الاستنتاجات: كان التعبير المنخفض لمستقبلات فيتامين د مرتبطا بورم النسيج الترويفي الحملي. بالمقابل، كان التعبيرالعالي لمستقبلات فيتامين د مرتبطا بالورم الحويصلي المائي. تشير هذه النتائج إلى أن مستويات مستقبلات فيتامين د قد تلعب دورا في شدة مرض النسيج الترويفي الحملي. Abstract: Objective: Vitamin D receptor (VDR) exerts anti-cancer properties in a variety of cancers. The purpose of this study was to investigate the expression of VDR in patients with hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). Methods: This is a cross-sectional study involved 61 specimens of HM (n = 37, 60.7%) and GTN (n = 24, 39.3%) was collected from the biopsy. An immunohistochemistry was used to asses the VDR expression. Student's t-test and Mann–Whitney test were used to compare the expression of VDR, including VDR staining intensity, VDR distribution, and histoscore, between HM and GTN tissue specimens. Results: No significant differences in age and parity were noted between patients with HM or GTN (p > 0.05). The VDR staining intensity of GTN tissue specimens was significantly lower than that of HM tissue specimens (2.3 ± 0.8 vs. 2.8 ± 0.5, p = 0.008). In addition, the histoscore for GTN tissues was significantly lower than that for HM tissues (7.3 ± 3.2 vs. 9.4 ± 28, p = 0.016). However, no significant differences in VDR distribution between GTN and HM tissues were observed (3.3 ± 0.8 vs. 3.3 ± 1.0, p = 0.525). Conclusion: Low VDR expression is associated with GTN, whereas high VDR expression is associated with HM, suggesting that the expression of VDR may regulate the severity of gestational trophoblastic disease.

Background: 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. Objectives: 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. Search Strategy: Seven predominant electronic databases were searched, including four English databases and three Chinese databases, from the inception of each database until January 31, 2023. Selection Criteria: 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. Data Collection and Analysis: 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. Main Results: 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). Conclusion: 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. Synopsis: Our study is the first to demonstrate that second curettage has a significant advantage over conventional chemotherapy in avoiding chemotherapy and in reducing chemotherapy courses. [ABSTRACT FROM AUTHOR]

Introduction: 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. Material and methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear. Materials and Methods: This case–control study included 57 GTN patients and 19 age‐matched patients with molar pregnancies (MP) in 2012–2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single‐agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared. Results: There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single‐agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single‐agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = −2.69, p = 0.007) but not at 24 months (Z = −1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4‐year pregnancy rate and the livebirth rate between the single‐agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single‐agent group (2.88 vs. 1.88 years). Conclusion: This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1–2 years after treatment or with other risk factors. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinicopathological features, prognostic factors, treatment, clinical response, and outcome of gestational choriocarcinoma (GCC). Materials and methods: A retrospective review was made of the clinicopathological and survival data of 13 patients who were diagnosed and treated for GCC in two referral centers in Turkey between 1992 and 2020. Results: The median age of patients was 36 years (range, 27–54 years), and seven were ≤39 years. The antecedent pregnancy was a term in nine (69.2%) cases, and the risk score was ≥7 in 11 (84.6%). According to the International Federation of Gynecology and Obstetrics 2009 staging, eight cases were in stage I, two in stage III, and three in stage IV. With the exception of one patient, all the others received combination chemotherapy (CT), and two of those were also treated with radiotherapy. Chemoresistance developed in 50% (6/12), and second‐line CT was given to four of these. The overall complete response rate was 69.2%. Four patients died of chemoresistance and disease progression, all of them were with antecedent‐term pregnancy, had high scores ≥7, and had metastases. Conclusion: GCC is a unique subtype of gestational trophoblastic neoplasia, which differs from others in terms of poor prognosis, a frequent tendency to early metastasis, and resistance to treatment. To be able to achieve the most efficient therapy and prognosis, histopathology‐based risk models should be developed. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic neoplasia (GTN) comprises a group of human neoplastic diseases that derive from fetal trophoblastic tissues. They are proliferative as well as degenerative disorders of placental elements and include complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) (90%), invasive mole (IM) (5-8%), which could also be metastatic, villous, or villous choriocarcinoma (CC) (1-2%), and placental site trophoblastic tumor (PSTT) (1-2%). We present three cases of GTN, two mimicking tuberculosis radiologically, and all three are associated with pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to play a diagnostic and predictive role in gestational trophoblastic disease. However, the conclusions are still ambiguous. This meta-analysis aimed to evaluate the combined predictive value of NLR and PLR in the malignant progression of gestational trophoblastic disease. Method: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and China Biomedical Literature Database were searched for the relevant literature published up to 1 October 2022. Study selection and data extraction were performed independently by two reviewers. All analyses were performed using Revman, MetaDisc and STATA software. Results: A total of 858 patients from five studies were included in this meta-analysis. The pooled sensitivity and specificity of NLR were 0.8 (95% CI: 0.71–0.88) and 0.73 (95% CI: 0.69–0.76), respectively, and the area under curve of the summary receiver operating curve was 0.81. The pooled sensitivity and specificity of PLR were 0.87 (95% CI: 0.75–0.95) and 0.49 (95% CI: 0.44–0.54), respectively, and the area under curve of the summary receiver operating curve was 0.88. I2 statistic and Deek's funnel plot showed no heterogeneity and publication bias. Conclusion: NLR can accurately predict the progression from hydatidiform mole to gestational trophoblastic neoplasia and is a promising biomarker in further follow-up. [ABSTRACT FROM AUTHOR]

Objectives. To monitor changes in serum anti-Mullerian hormone (AMH) levels of the patients with gestational trophoblastic neoplasia (GTN) who have undergone uterine preservation during treatment with a Methotrexate (MTX) regimen and associations with AMH variations. Methods. This observational prospective cohort study included 35 patients with low-risk GTN with uterine preservation during single-agent MTX chemotherapy at Hanoi Obstetrics and Gynecology Hospital from August 2021 to August 2022. Serum AMH levels were measured before initiation of chemotherapy and after the 1st, 2nd, and 3rd chemotherapy cycles. AMH evolution and its associations with some factors were analyzed. Results. The median basal AMH level before chemotherapy was 2.87 ng/mL (0.96 - 7.9 ng/mL) and negatively correlated with age. The serum AMH levels decreased significantly after each chemotherapy cycle (2.87 vs. 1.16, 0.91, 0.41 ng/mL). The median magnitude of the AMH levels decline after 1st, 2nd, and 3rd chemotherapy cycles were 51.2%, 69.4%, and 84.6% (p<0.001), respectively. AMH variation was associated with the basal AMH level, but not with age, ßhCG at diagnosis and menstrual status. Conclusion. Our study has shown that the serum AMH levels declined rapidly and steadily in all patients during chemotherapy for GTN. Although AMH cannot be used to monitor fertility potential lonely, these new studies improve our knowledge of ovarian toxicity and ovarian reserve during chemotherapy and strongly support the use of fertility preservation strategies. [ABSTRACT FROM AUTHOR]

Background/Aim: 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. Case Report: A 43-yearold patient received pulse actinomycin D treatment for postmolar 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. Conclusion: Surgical resection should be considered a viable therapeutic strategy for uterine polypoid growth in chemotherapy-resistant low-risk GTN. [ABSTRACT FROM AUTHOR]

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Key Clinical Message In young women presenting with atypical features of intracerebral hemorrhage, metastatic choriocarcinoma should be considered as a differential diagnosis. In resource‐poor settings, a high index of suspicion and serum β‐hCG are crucial for diagnosis. Abstract Intracerebral hemorrhage in the young is rarely caused by metastatic choriocarcinoma. Diagnosis of this condition may be particularly challenging in resource‐poor settings where access to diagnostic technologies may be limited. We present a case series of three young females diagnosed with metastatic choriocarcinoma after initially presenting with intracerebral hemorrhage, each demonstrating unique clinical manifestations. We aim to highlight the diagnostic considerations in the management of this infrequently encountered cause of intracerebral hemorrhage, especially in resource‐constrained settings. Case 1 involved a 21‐year‐old woman who was initially diagnosed with intracerebral hemorrhage likely of tumoral origin from an unknown primary source. Further evaluation revealed extremely high levels of β‐hCG and features suggestive of an intrauterine malignancy, which led to a diagnosis of metastatic choriocarcinoma. This further became complicated by pulmonary embolism. Unfortunately, she succumbed to respiratory failure during treatment. Case 2 is a young woman who presented to the emergency unit and was managed as a case of lobar intracerebral hemorrhage. Further checks revealed a previous history of hysterectomy done on account of placental site trophoblastic tumor, which promoted an evaluation for choriocarcinoma. Case 3 involved a 20‐year‐old patient who initially presented with headache and vomiting. An enhanced magnetic resonance imaging showed a large subacute right temporal occipital subependymal hemorrhage with mass effect. After probing further, we discovered that she underwent exploratory laparotomy for suspected ruptured ectopic gestation, which later turned out to be a gestational trophoblastic neoplasia. After further evaluation a diagnosis of choriocarcinoma with brain metastasis. Our case series emphasizes the importance of having a high index suspicion in young females who present with atypical features of ICH. The varied clinical scenarios highlight the challenges in diagnosing young females. It also underscores the critical role of serum β‐hCG, especially in resource‐limited settings where biopsies are not readily available. Building a repository of these diverse manifestations is essential for increasing the index of suspicion and ultimately improving patient outcomes.

Gestational trophoblastic neoplasia (GTN) is extremely rare, but has a very good prognosis, with a cure rate close to 100%, for low-risk diseases. This article describes the case of a healthy 28-year-old nulliparous patient with GTN resistant to multiple lines of treatment. The era of immunotherapy is revolutionizing oncology, having already proved its worth in the treatment of many cancers. This article will have a specific focus on the emerging role of immunotherapy in the treatment of GTN. Unfortunately, the use of an immune checkpoint inhibitor (ICI) failed in our case, emphasizing on the necessity to clearly define the future role of immune therapy in GTN. Finally, given the rapid progression of the disease after hysterectomy, induction with Paclitaxel- Ifosfamide and then intensification with high-dose Carboplatin and Etoposide with peripheral blood stem cell support was given as a rescue therapy with still curative intent.

Gestational trophoblastic neoplasia (GTN) comprises a group of human neoplastic diseases that derive from fetal trophoblastic tissues. They are proliferative as well as degenerative disorders of placental elements and include complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) (90%), invasive mole (IM) (5–8%), which could also be metastatic, villous, or villous choriocarcinoma (CC) (1–2%), and placental site trophoblastic tumor (PSTT) (1–2%). We present three cases of GTN, two mimicking tuberculosis radiologically, and all three are associated with pulmonary embolism.

A 38-year-old female with an etonogestrel implant in place and history of previous ectopic pregnancy presented with acute abdominal pain and vaginal bleeding. She was found to have a beta-hCG of >12,000 mIU/mL and free fluid noted on a focused assessment with sonography in trauma exam. She underwent an emergent diagnostic laparoscopy due to the suspicion of a ruptured ectopic pregnancy. Findings at the time of surgery included a normal-appearing uterus and left fallopian tube, a surgically absent right fallopian tube and large volume hemoperitoneum with a rapidly expanding left retroperitoneal hematoma. A postoperative computerized tomography (CT) angiogram suggested active bleeding from a pseudoaneurysm of the left renal artery which was successfully embolized by interventional radiology. Biopsy confirmed gestational trophoblastic neoplasia (GTN) after metastases to the brain. In this report, we describe the details of this case of GTN with an atypical presentation.

Background: The incidence of molar pregnancy has demonstrated marked geographic and ethnic differences. This difference in the prevalence across various countries perhaps may depend upon the socioeconomic, genetic, nutritional and other cultural factors. In spite of having a higher prevalence among Asians, still epidemiological characteristics of Gestational Trophoblastic Disease (GTD) or Gestational Trophoblastic Neoplasia (GTN) are difficult to determine secondary to inconsistencies in case definitions and lack of centralised databases. Hence, this study was undertaken to determine the proportion and the clinical profile of women with hydatidiform mole from a South Indian population, where as of now there is limited data to enable us to detect and provide the standard of care for patients with GTN. Materials and Methods: A prospective cohort study between August 2014 to December 2015 and a retrospective review of medical records for the preceding 2 years from the year 2012 to 2014 was conducted in JIPMER to determine the proportion of women with molar pregnancy as well as to study the clinico-epidemiologic profile of hydatidiform mole. The study population comprised of a total of 116 cases, of which, 68 cases belonged to the prospective group and 48 cases to the retrospective group. The patients belonging to the prospective group (68) were followed up for a period of 6 months to note the trend of the β HCG and to detect the occurrence of GTN. The patients in the retrospective group (48) were considered only for analysing the clinical profile of hydatidiform mole, as follow up was not possible for this group of patients. Results: The proportion of molar pregnancy was calculated to be 2.07 per 1000 live births. Majority (59%) of the study population belonged to the age group of 18-23 years. Almost all the patients (98%) belonged to lower socioeconomic group. More than one-third (48%) of the patients were nulliparous. It was observed that, greater than half of the patients (56%) presented between 11-15 weeks of amenorrhoea. Majority (76%) of the patients had no previous abortions in their obstetric history. Only 4 (3.45%) patients had previous history of molar pregnancy. Abnormal uterine bleeding was the most common complaint noted in 79% of patients. Nausea and vomiting were noted in 62 patients, out of which 25 (40%) presented with hyperemesis requiring fluid and electrolyte correction. Anaemia was the most common medical complication noted in 55% of patients, followed by hyperthyroidism in 33% and hypertension in 2% patients. Among the 116 patients, 74(64%) had preevacuation HCG level more than 2,00,000mIU/ml. Suction evacuation was done in all the cases and 9 (8%) patients required re-evacuation in view of residual vesicular mole on a check scan. Among the 116 patients, histopathology revealed complete mole in 88% patients and partial mole in 12%. In the prospective group, following suction evacuation, 79% of the patients attained remission by the end of 6 months whereas in 13 patients (21%), hCG continued to either plateau or increase following the primary evacuation and they further developed GTN requiring chemotherapy. Out of the 13 cases of GTN, 7 patients attained remission with chemotherapy, whereas 6 patients failed to achieve remission during the 6 months' study period. Conclusion: Young, nulliparous women belonging to low socio-economic status had a higher proportion of hydatidiform mole. Improving the literacy rates, creating awareness among the women, early registration of pregnancy, prompt referral to higher centres and early administration of appropriate treatment, with a vigilant follow up would help in early detection of GTN.There is also a need for studies at country level which will give us a national figure on molar pregnancies. Thus, a standardized clinicoepidemiological profile of molar pregnancy in India can be created. [ABSTRACT FROM AUTHOR]

The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management. Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset. Three streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms. Our streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended. • The FIGO scoring system in GTN patients can be streamlined from eight risk factors to two. • Three logistic regression models containing two risk factors match FIGO performance across several performance measures. • Models favoured for ongoing validation are: • Model 2 (M2): pre-treatment hCG + site of metastases; and • Model 3 (M3): pre-treatment hCG + number of metastases. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN). Methods: We performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU. The clinical characteristics, adverse events, and response rates were compared between the groups. Results: The patients in the FPV and FAV groups received a total of 228 and 190 courses of chemotherapy, respectively. Complete response (CR) was found in 88.89% (48/54) and 90.48% (38/42) of patients in the FPV group and FAV group, respectively (p = 0.801). Both chemotherapy regimens yielded CR in all low-risk patients (100% vs. 100%), whereas 86.67% and 88.24% of high-risk patients achieved CR (FPV vs. FAV, p = 0.836), respectively. The most common adverse events (AEs) were myelosuppression and gastrointestinal reactions including neutropenia (83.97%), anemia (60.05%), and nausea (46.41%). In comparison to those in the FAV group, patients in the FPV group reported higher rates of grade 1/2 nausea (53.51% vs. 37.89%, p = 0.001), hepatotoxicity (28.95% vs. 17.89%, p = 0.008), oral mucositis (23.25% vs. 10.53%, p = 0.001), and grade 3/4 neutropenia (47.37% vs. 27.37%, p < 0.001), while grade 1/2 diarrhea (7.46% vs. 13.68%, p = 0.037) and grade 3/4 oral mucositis (0 vs. 6.32%, p < 0.001) were much more common in the FAV group. The rate of overall survival at 5 years was 96.8% in the FPV group and 97.3% in the FAV group (p = 0.760), whereas the 5-year disease-free survival rates were 95.9% and 93.9% (p = 0.754), respectively. Conclusion: The FPV and FAV regimens with pulsed intravenous 5-FU yielded comparable CR rates and tolerability in patients with GTN with FIGO scores of >5. Further randomized controlled trials are warranted to validate their efficacy. [ABSTRACT FROM AUTHOR]

Abstract Introduction Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear. Materials and Methods This case–control study included 57 GTN patients and 19 age‐matched patients with molar pregnancies (MP) in 2012–2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single‐agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared. Results There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single‐agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single‐agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = −2.69, p = 0.007) but not at 24 months (Z = −1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4‐year pregnancy rate and the livebirth rate between the single‐agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single‐agent group (2.88 vs. 1.88 years). Conclusion This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1–2 years after treatment or with other risk factors.

Introduction Triploid partial molar pregnancies are not viable, and confer maternal risks including preeclampsia, hemorrhage, gestational trophoblastic neoplasia, and trophoblastic embolization. We report a case managed expectantly until 26 weeks' gestation in a patient requesting continuation of pregnancy.

Abstract Background Multiple studies have confirmed that programmed cell death 1 (PD‐1) and programmed cell death ligand 1 (PD‐L1) is widely expressed in gestational trophoblastic neoplasia (GTN) tissues. Therefore, immune checkpoint inhibitors may be an option for the treatment of recurrent and drug‐resistant GTN. Case Four patients with recurrent or drug‐resistant GTN who were treated with PD‐1/PD‐L1 checkpoint inhibitor agents combined with chemotherapy were reported. The mean age of recurrence was 45.8 years (35–56 years), including three cases of choriocarcinoma (CC) and one case of invasive mole (IM). International Federation of Gynecology and Obstetrics (FIGO) prognosis score: ≤6 (low risk) in one case, 7–12 (high risk) in one case, ≥13 (very high risk) in two cases. There were two cases of lung metastasis and one case of vulvar and inguinal lymph node metastasis. One of the four patients underwent total hysterectomy and one patient underwent resection of lung metastases. All the four patients received comprehensive treatment of immunotherapy combined with chemotherapy after relapse, among which one patient achieved complete response (CR), two patients achieved partial response (PR), and one patient developed progressive disease (PD). Three patients who achieved PR or CR were maintained by single agent immunotherapy after combination therapy, and there was no disease recurrence during follow‐up. One patient with PD also achieved CR after using salvage chemotherapy after recurrence, and there was no disease recurrence during follow‐up. During the treatment, four patients had different degrees of immune‐related adverse reactions, all of which were grade I‐II, and no severe adverse reactions were found. Conclusion Immune checkpoint inhibitors combined with chemotherapy has an impressive therapeutic effect on recurrent or drug‐resistant GTN with mild adverse reactions, which can be used as a treatment option for such patients. However, due to the lack of large sample data support, the specific time and treatment course of its use, long‐term use of adverse reactions and whether it affects fertility function remain to be solved.

Gestational trophoblastic disease (GTD) is a heterogenous group of disorders assosiated with abnromal proliferation of trophoblast and their course is characterized by varying degrees of malignancy. WHO classified GTD into three categories: tumor-like lesions, molar pregnancies and gestational trophoblastic neoplasms.HM is characterized by abnormal proliferation of both syncytiotrophoblast and cytotrophoblast, edema of placental villi, with or without the presence of a fetus. Complete and partial moles have been classified as two separate disease entities, and their division depends on the genetic material they contain. The complete mole has a complete set of chromosomes coming only from paternal genome, while the partial mole is triploid and the genetic material transferred comes from the father and the mother. Post-molar gestational trophoblast neoplasia (GTN) is a clinical diagnosis based on the observation of a persistent increase or persistently high hCG concentration after evacuation of the mole, requiring evaluation and treatment. Invasive hydatidiform mole, together with choriocarcinoma and placental tumor, belong to gestational trophoblast neoplasia. Currently, research has shown that short tandem repeat (STR) genotyping is the gold standard for making the correct diagnosis and this test should be performed if possible. GTD diseases originate from both syncytiotrophoblast and cytotrophoblast tissues and as a result of which they produce an extremely sensitive marker -human chorionic gonadotropin. The facts stated above and significant sensitivity to chemotherapy mean that the average cure rate for this disease currently exceeds 90%. Although the main treatment of gestational trophoblast neoplasia involves the use of cytostatics in cases with worse prognosis, i.e. those with a higher risk, surgery turns out to be an invaluable treatment method.

Objective: Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) that originates from abnormal trophoblast proliferation. Although chemotherapy is effective for choriocarcinoma, personalized treatment becomes essential when patients develop chemoresistance. Here, we present the clinical course of a case of intractable choriocarcinoma that achieved complete remission with pembrolizumab following cytotoxic chemotherapy. Case report: A 38-year-old woman was initially diagnosed with low-risk GTN and treated with single- and multi-agent chemotherapy. She underwent a hysterectomy and was diagnosed with pathological choriocarcinoma with high-risk GTN. She was treated with multiple courses of several chemotherapy regimens. However, she did not achieve remission. Her choriocarcinoma showed high microsatellite instability; therefore, she took ten courses of pembrolizumab, but her hCG value increased. Subsequently, she underwent eight courses of paclitaxel and carboplatin alternating with paclitaxel and etoposide and achieved remission. Conclusion: This case suggests that pembrolizumab may improve the efficacy of subsequent chemotherapy.

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