Study and treatment of gestational trophoblastic diseases at the John I. Brewer Trophoblastic Disease Center, 1962-1990.

From 1962 through 1989, 5063 patients were referred to the John I. Brewer Trophoblastic Disease Center of the Northwestern University Medical School. Among these were 564 patients treated with chemotherapy for gestational trophoblastic tumors (choriocarcinoma and invasive mole). The overall cure rate was 94%, 100% for 323 patients without evidence of metastases and 85% for 241 patients with metastatic disease. Four factors were determined to significantly influence treatment response: (1) clinicopathologic diagnosis of choriocarcinoma, (2) metastases to sites other than the lung or vagina, (3) number of metastases, and (4) previous failed chemotherapy.     

The changing role of thoracotomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center

OBJECTIVE: To review our experience with thoracotomy in gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Nineteen thoracotomy patients from our database were identified. Thoracotomy was performed for therapeutic reasons in 11 patients and to clarify the diagnosis in eight. RESULTS: Among the 11 patients with chemotherapy-resistant pulmonary tumors, 10 of 11 (90.9%) achieved remission with thoracotomy. Thoracotomy was more likely to be done to clarify diagnosis before 1980 (83%) than after 1980 (23%) (p = 0.04), when it became more likely to be done for therapeutic indications. Ten patients had solitary lung lesions and 9 had multiple lesions. Four patients died (21%), with an average survival after thoracotomy of 149 days; patients had bilateral or multiple lung lesions, median preoperative hCG was 58,000 mIU/mL and all were stage IV. Survivors had lower stage disease, were more likely to have solitary lesions and had lower preoperative hCG levels. CONCLUSION: There have been several temporal changes in the indications for thoracotomy for GTN. In general, the optimal patient to achieve remission with thoracotomy will have stage III disease, a preoperative hCG of < 1,500 mIU/mL, and a solitary lung nodule resistant to chemotherapy. Likelihood of remission after thoracotomy is high in properly selected patients.     

Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: The New England Trophoblastic Disease Center experience

Objectives

To assess the outcomes and toxicity of first-line methotrexate (MTX) chemotherapy in low-risk postmolar gestational trophoblastic neoplasia (GTN) patients receiving 8-day methotrexate or one-day methotrexate infusion regimens.

妊娠滋养细胞肿瘤治疗后肺内阴影持续存在患者的预后分析

目的 分析妊娠滋养细胞肿瘤肺转移患者经规范治疗后,血人绒毛膜促性腺激素13亚单位（13．hCG）水平降至正常,但肺内阴影持续存在患者的预后。方法 1985年1月至2004年1月间北京协和医院共收治了妊娠滋养细胞肿瘤患者1130例,其中获得完全缓解（CR）患者901例,获得部分缓解（PR）患者187例。901例CR患者中合并肺转移者463例;187例PR患者中152例经规范化疗后血β-hCG水平降至正常,但肺内转移灶未完全吸收而带瘤出院随诊。本研究对上述152例肺内带瘤出院患者的临床资料进行回顾性分析,并分别与同期出院的901例CR患者以及合并肺转移的463例CR患者的预后进行比较。结果 152例患者均接受了规范的多疗程多药联合化疗1．30个疗程（平均3．6个疗程）后血β-hCG水平降至正常,然后又接受了0—8个疗程（平均3．7个疗程）的巩固化疗而带瘤出院。152例肺内带瘤出院患者中,除17例患者未随诊外,其余135例患者均定期随诊,随诊时间为14—110个月。其中,83例患者随诊期间肺内阴影没有明显变化;46例患者肺内阴影消失或缩小;6例（均为绒毛膜癌）患者在停药6—8个月后血β-hCG水平升高,病情进展。152例肺内带瘤出院患者的病情进展率为3．9％（6／152）,分别与901例CR患者的复发率[3．4％（31／901）]以及463例合并肺转移CR患者的复发率[2．2％（10／463）]比较,差异均无统计学意义（P〉0．05）。结论 妊娠滋养细胞肿瘤肺转移患者经规范治疗后血β-hCG水平降至正常,再经过2．4个疗程的巩固化疗后其肺内阴影不再继续缩小或消失者,多为肺内转移灶坏死或局部纤维化,可以认为其为CR。但出院后应密切随诊,尤其是停药6个月左右的绒毛膜癌患者。     

Low-risk gestational trophoblastic neoplasia outcome after treatment with VMP regimen from 2005 to 2017

ObjectiveTo evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital.Materials and methodsBetween 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis.ResultsThe first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4.ConclusionFor patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission.     

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984)

Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1.1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.     

The prognosis of gestational trophoblastic neoplasia patient with residual lung tumor after completing treatment

OBJECTIVE: To analyze retrospectively the prognosis of gestational trophoblastic neoplasia (GTN) patients who achieved normal beta-hCG titer after completing treatment but remained with residual lung tumor. METHOD: A total of 1,130 GTN patients were hospitalized at Peking Union Medical College Hospital from January 1985 to January 2004. Among these patients, 901 achieved complete remission (CR); 152 achieved normal blood beta-hCG titer after the completion of treatment but remained with residual lung tumor (defined as partial remission). Retrospective analyses were carried out on the 152 patients. Statistical analysis was used to compare the recurrent rate of the CR patients with the progression rate of the 152 patients. RESULT: 17 of the 152 patients lost follow-up. Of the rest 135 patients followed up from 14 to 110 months, 83 showed no significant changes as to their residual tumors; 46 patients' residual tumors diminished or disappeared; and the other 6 patients got progression of disease (PD), with beta-hCG level going up 6-8 months after completing treatment. There is no significant statistical difference (P > 0.05) between the recurrent rate of the 901 CR patients and the progression rate of the 152 patients. There is also no significant statistical difference (P > 0.05) between the recurrent rate of the CR patients with lung metastasis and the progression rate of the 152 patients. CONCLUSION: After achieving normal beta-hCG titer, patients whose lung tumor stayed unchanged even following several additional courses of chemotherapy should be considered as CR patients. Follow-ups should be strictly carried out on these patients, especially at around 6 months after the completion of treatment, and particularly for high-risk and drug-resistant choriocarcinoma (CC) patients.     

Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy

OBJECTIVE: To evaluate the efficacy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in the primary treatment of metastatic high-risk gestational trophoblastic neoplasia. STUDY DESIGN: Thirty women with metastatic high-risk gestational trophoblastic neoplasia were treated primarily with EMA-CO between 1986 and 2005. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing etoposide and a platinum agent with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response and factors affecting treatment success were analyzed retrospectively. RESULTS: The overall survival rate was 93.3% (28 of 30). Of the 30 patients treated with EMA-CO, 20 (66.7%) had a lasting clinical response, 8 (26.7%) developed resistance but were subsequently placed in remission with platinum-based chemotherapy, and 2 (6.7%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by human chorionic gonadotropin level (<100,000 mIU/ mL, 82%, vs. > 100,000 mIU/mL, 46%), metastatic site (lung and pelvis, 75%, vs. other, 33%) and International Federation of Gynecology and Obstetrics (FIGO) risk factor score (< 7, 92% vs. >7, 50%). Surgical procedures were performed on 12 patients, and 4 patients received brain irradiation. Eight (80%) of 10 patients who received secondary platinum-based chemotherapy or without surgery were cured. The 2 patients who died had stage IV disease (brain and/or liver metastases) with FIGO scores of 13 and 14. CONCLUSION: Over 93% of 30 patients with metastatic high-risk gestational trophoblastic neoplasia treated initially with the EMA-CO protocol, often in conjunction with brain irradiation, surgical resection of sites of persistent tumor and salvage platinum-based chemotherapy, were cured.     

耐药和复发性妊娠滋养细胞肿瘤的临床病例分析

目的 总结分析耐药和复发性妊娠滋养细胞肿瘤(GTN)的临床特点和治疗效果.方法 回顾性分析2005年1月至2007年12月间,北京协和医院收治的难治性GTN患者的临床资料.并对既往治疗过程中血清人绒毛膜促性腺激素β亚单位(β-hCG)水平达到正常水平,而在停化疗3个月内开始再次升高且除外再次妊娠的患者(不确定组),分别与文献中普遍承认的既往治疗过程中血清β-hCG水平从未达到过正常的耐药组、及既往治疗过程中血清β-hCG水平达到正常水平而停化疗3个月后开始再次升高且除外再次妊娠的复发组的临床特点及治疗效果进行比较.结果 因既往治疗失败而转诊至本院的难治性GTN患者共81例,其中耐药组38例,不确定组32例,复发组11例.不确定组、耐药组患者的既往化疗方案种类的中位数、血清学完全缓解率、治疗过程中因化疗效果不满意更改方案率及总体更改方案率分别为2.3和3.1个、100%(32/32)和66%(25/38)、22%(7/32)和58%(22/38)、28%(9/32)和63%(24/38),两组分别比较,差异均具有统计学意义(P＜0.05).而不确定组的32例患者与复发组的11例患者相比,其临床特点(包括年龄、末次妊娠性质、妊娠终止至化疗开始的时间间隔、转移部位、预后评分)、既往治疗情况(包括既往化疗的疗程数和方案种类数)、本院首选化疗方案、手术治疗情况、更改化疗方案情况及治疗结局间均无差异(P＞0.05).结论 为准确评价难治性GTN患者的治疗效果,对于因血清β-hCG水平达到完全缓解后,在停止治疗3个月内发生血清β-hCG水平再次升高、且排除再次妊娠的患者,归为复发病例更为合适,复发与停止治疗后的时间长短无关.与耐药患者相比,复发患者的预后较好.     

Weekly intramuscular methotrexate in the treatment of low-risk gestational trophoblastic neoplasia

Objective  

The objective of this study was to determine the efficacy of weekly intramuscular (IM) methotrexate without dose escalation as first-line chemotherapy for low-risk gestational trophoblastic neoplasia (LRGTN).     

The management of recurrent and drug-resistant gestational trophoblastic neoplasia (GTN)

Gestational trophoblastic neoplasia (GTN) comprises a spectrum of disease from low-risk disease which can be cured with simple relatively non-toxic treatment, to extremely aggressive tumours which require specialized management. The prognostic variables in patients with GTN are different from those in other gynaecological malignancies, and the major adverse prognostic variables include long interval from antecedent pregnancy, high concentrations of the pregnancy hormone, human chorionic gonadotrophin, metastases in brain and liver and failure of prior treatment. Patients who relapse after their prior treatment can also be categorized into different risk groups. Salvage treatment can vary from single agent actinomycin D to combination chemotherapy and, in selected cases, surgery. With appropriate management, the majority of patients can achieve long-term remission and, in most cases, preserve fertility. The late side-effects of more intensive treatment are a small risk of inducing second tumours and also of bringing forward the age of menopause.     

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979–1984)

Summary. Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1·1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.     

放射血管介入技术在妊娠滋养细胞肿瘤诊治中的价值

妊娠滋养细胞肿瘤具有极强的亲血管性生物行为,放射血管介入技术通过将导管插入脏器的营养血管,不仅能够定位肿瘤病灶,而且还能够发现出血病灶,并对其进行相应的治疗。通过复习文献,讨论了放射血管介入技术在妊娠滋养细胞肿瘤诊治中的应用价值。     

25 years' experience in the treatment of gestational trophoblastic neoplasia in Hungary

OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexate/folinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy.     

Assessment of the response to chemotherapy in gestational trophoblastic neoplasia with vaginal metastases

Background and goals  This study is designed to survey gestational trophoblastic neoplasia with vaginal metastases (GTN + VM) manifestations, prognosis and chemotherapy response in order to consider appropriate chemotherapy regimen for these patients. There have been just a few studies about treatment of GTN + VM. Materials and methods  Patients with Stage III GTN with or without vaginal metastases who had referred to Vali-e-Asr Hospital during 1996–2006 have been selected to take part in this study and the size of metastases was measured. Then response and resistance to single and combination chemotherapy regimens have been compared in these two groups. The data were processed using SPSS system (release 10). Statistical analysis was done with X² to determine factors associated with complete clinical response. The level of significance was assigned at P < .05. Results  Forty-eight patients with stage III (with pulmonary metastases) GTN patients have been selected, 13 with vaginal metastases and 35 without vaginal metastases. Incidence of vaginal metastases in stage III was 26%. Metastases were mainly in distal part of vagina and suburethra. Chief complaint was severe hemorrhage in 25% of patients and was controlled by vaginal packing with just one exception. Group of vaginal metastases showed 66.6% resistance to first-line chemotherapy, compared to 28.6% in patients with no vaginal metastases (P-value = 0.010). Median of chemotherapy courses in low-risk vaginal metastatic patients was 5 (mean = 5.2), compared to three courses in the group without vaginal metastases. Resistance to single chemotherapy was significantly higher in GTN + VM versus GTN without VM patients and resistance was higher especially in patients with metastases with more than 3 cm (in diameter). Conclusions  Vaginal metastasis with more than 3 cm in diameter is an important prognostic factor in GTN patients. There have higher risks for severe hemorrhage and resistance to single agent chemotherapy, so in these patients combination chemotherapy, with no regard to staging and scoring, would be a better choice. An erratum to this article can be found at