Experiences of Women With Gestational Trophoblastic Neoplasia Treated With High-Dose Chemotherapy and Stem Cell Transplantation: A Qualitative Study.

PURPOSE/OBJECTIVES: To explore the experiences of women with gestational trophoblastic neoplasia during and after treatment to understand their perspectives, priorities, and concerns.
. RESEARCH APPROACH: A descriptive, exploratory study using in-depth semistructured interviews.
. SETTING: All interviews were conducted in a quiet, designated room at Weston Park Hospital in Sheffield, South Yorkshire.
. PARTICIPANTS: Women with gestational trophoblastic neoplasia who had received stem cell transplantation from 2003 to 2013. Ten patients were eligible, and eight agreed to participate.
. METHODOLOGIC APPROACH: Interviews were carried out over the phone and were recorded and transcribed verbatim. Framework analysis was carried out to generate in-depth descriptions of participants' experiences.
. FINDINGS: Participants described significant physical, psychological, and social effects during and following treatment. Recovery was slow, and treatment had long-term effects on sexuality and body image. The impact of the women's diagnosis and treatment on their children was a primary concern.
. INTERPRETATION: The study provided insight into the multidimensional impact of stem cell transplantation, which can continue after treatment. The need for family-centered services for patients with dependent children was identified.
. IMPLICATIONS FOR NURSING: Nurses need to develop services that effectively communicate the challenges of stem cell transplantation to patients and provide family-centered care and late effects and rehabilitation services.

Dutch Risk Classification and FIGO 2000 for Gestational Trophoblastic Neoplasia Compared.

OBJECTIVE: Over the years, there has been a wide variety of classification systems in use worldwide to stratify patients between single-agent versus multi-agent chemotherapy, hindering comparison of international research results. The study presents a retrospective comparison of the International Federation of Gynecology and Obstetrics 2000 and Dutch risk classification system for gestational trophoblastic neoplasia. METHODS AND MATERIALS: All patients diagnosed with gestational trophoblastic neoplasia between January 2003 and December 2012 at the trophoblastic disease centre in London were retrospectively scored according to the Dutch classification system (N = 813). RESULTS: An extensive overlap between both scoring systems was seen, even though items and relative value of items were quite distinct. The Dutch system seems to be simpler and easier to apply in all situation; a degree of overtreatment can however be presumed with the use of either system. CONCLUSIONS: Although it is likely that outcome is indeed affected by the individual factors used in both systems, many factors relate to tumor bulk and may not be independently prognostic. We therefore believe that further refinement of the classification systems and their underlying prognostic items plus any new items that seem promising would be useful.

EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis.

PURPOSE: Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010). PATIENTS AND METHODS: Patients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m(2) and cisplatin 20 mg/m(2) (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted. RESULTS: Four hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort. CONCLUSION: OS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN.

Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study.

BACKGROUND: Indications for chemotherapy in gestational trophoblastic disease include raised human chorionic gonadotropin (hCG) concentrations 6 months after uterine evacuation of hydatidiform mole, even when values are falling. We aimed to establish whether chemotherapy is always necessary in these patients. METHODS: We retrospectively identified women registered between January, 1993, and May, 2008, at Charing Cross Hospital, London, UK, who had persistently high hCG concentrations 6 months after evacuation of hydatidiform mole. Rates of hCG normalisation, relapse, and death were assessed in patients continued under surveillance and those who received chemotherapy after 6 months. We postulated that a surveillance policy would be clinically acceptable if hCG values returned to normal in 75% of patients or more. FINDINGS: 76 (<1%) of 13,960 patients with hydatidiform moles had persistently high hCG concentrations of more than 5 IU/L 6 months after evacuation. 66 (87%) patients continued under surveillance and hCG values spontaneously returned to normal without chemotherapy in 65 (98%) of these patients. Values in one patient did not become normal because of chronic renal failure, but she remains healthy. Ten patients received chemotherapy, and hCG concentrations returned to normal in eight (80%) of these individuals (surveillance vs chemotherapy groups p=0·044) and remained slightly high (6-11 IU/L) in two without any associated clinical problems off treatment. We noted no significant differences between individuals in the surveillance and chemotherapy groups, apart from lower median hCG concentrations 6 months after evacuation in those under surveillance than in those given chemotherapy (13 IU/L, range 5-887, vs 157 IU/L, range 6-6438; p=0·004). Overall, there were no deaths in this series. INTERPRETATION: A surveillance policy seems to be clinically acceptable in patients with low and declining concentrations of hCG 6 months after evacuation of hydatidiform mole. FUNDING: National Commissioning Group, Imperial Experimental Cancer Medicine Centre, Imperial Biomedical Research Centre, and Cancer Research UK.

Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.

BACKGROUND: Placental-site trophoblastic tumours are a rare form of gestational trophoblastic disease and consequently information about optimum management or prognostic factors is restricted. We aimed to assess the long-term outcome of stage-adapted management by surgery, chemotherapy, or both for patients with the disorder. METHODS: 35 550 women were registered with gestational trophoblastic disease in the UK (1976-2006), of whom 62 were diagnosed with placental-site trophoblastic tumours and included, retrospectively, in the study. Patients were treated by surgery, chemotherapy, or both. We estimated the probabilities of overall survival and survival without recurrence of disease 5 and 10 years after the date of first treatment, and calculated the association of these endpoints with prognostic factors, including time since antecedent pregnancy, serum concentration of beta-human chorionic gonadotropin, and stage of disease, with both univariate and multivariate analyses. FINDINGS: Probabilities of overall and recurrence-free survival 10 years after first treatment were 70% (95% CI 54-82) and 73% (54-85), respectively. Patients with stage I disease had a 10-year probability of overall survival of 90% (77-100) and did not benefit from postoperative chemotherapy. By contrast, patients with stage II, III, and IV disease required combined treatment with surgery and chemotherapy; probability of overall survival at 10 years was 52% (3-100) for patients with stage II disease and 49% (26-72) for stage III or IV disease. Outcome for patients who had recurrent or refractory disease was poor: only four (22%) patients achieved long-term survival beyond 60 months. Multivariate analysis showed that the only significant independent predictor of overall and recurrence-free survival was time since antecedent pregnancy. A cutoff point of 48 months since antecedent pregnancy could differentiate between patients' probability of survival (<48 months) or death (>/=48 months) with 93% specificity and 100% sensitivity, and with a positive predictive value of 100% and a negative predictive value of 98%. INTERPRETATION: Stage-adapted management with surgery for stage I disease, and combined surgery and chemotherapy for stage II, III, and IV disease could improve the effectiveness of treatment for placental-site trophoblastic tumours. Use of 48 months since antecedent pregnancy as a prognostic indicator of survival could help select patients for risk-adapted treatment. FUNDING: National Commissioning Group.

Practical issues in the management of low-risk gestational trophoblast tumors.

Using data primarily from Charing Cross Hospital in London, we examined the organization and funding of patients' care and follow-up, the value of second evacuations, the indications for treatment escalation and the results of treating patients with persistent low levels of human chorionic gonadotropin (hCG) following a molar pregnancy. In the U.K. system the total cost per patient treated is approximately $30,000. Second evacuations appear to have only a modest chance (18%) of benefit in patients with hCG levels over 5,000 IU/L. Outcome analysis of patients with low-risk gestational trophoblastic tumor (GTT) treated with methotrexate/folinic acid indicates that hCG levels in excess of500 IU/L at 7 weeks after starting are an accurate predictor of impending methotrexate resistance. For patients with hCG values under 100 IU/L at the time of treatment, a review of the 30 most recent low-risk GTT patients demonstrates a 100% cure rate with standard treatment. Low-risk GTT following a molar pregnancy is a highly curable malignancy, and cure rates approaching 100% should be expected. National or regional organization of follow-up and treatment is simple, economic and associated with enhanced outcomes when appropriate treatment policies are followed.

Management and outcome of healthy women with a persistently elevated beta-hCG.

PURPOSE: Raised serum beta human chorionic gonadotrophin (beta-hCG) not due to pregnancy can occur as a consequence of (1) gestational trophoblastic neoplasia (GTN), (2) non-gestational trophoblastic tumours, (3) a false-positive beta-hCG, (4) the menopause or (5) a high normal level. Accurate differentiation between these causes is vital to avoid potentially inappropriate investigations and therapies, which may induce infertility or other serious adverse events. Here we report the United Kingdom experience of patients with an elevated beta-hCG of initial uncertain cause and provide a clinical algorithm for the management of such cases. METHOD: The Charing Cross and Weston Park Hospital GTN databases were screened to identify patients referred with an elevated beta-hCG who were not pregnant and had no previous diagnosis of GTN. RESULTS: Between 1981 and 2004 fourteen women presented with persistently raised serum beta-hCG resulting in diagnostic problems. False-positive beta-hCG was excluded in all. Three patients developed gestational choriocarcinoma after 9-29 months. However, in 11 women no cause for the persistently elevated beta-hCG was found. One of these achieved chemotherapy-induced normalisation of serum beta-hCG, but the remaining 10 underwent surgery and/or chemotherapy without benefit. Thus, 71% (10/14) of patients remain well with unexplained elevated beta-hCG levels. CONCLUSION: Elevated serum and urinary beta-hCG levels in healthy women should be investigated systematically to exclude an underlying malignant process and to avoid inappropriate surgical and medical intervention. Long-term follow-up is required as tumours may not become apparent for many months or years.

Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin.

We assessed 77 twin pregnancies, comprising complete hydatidiform mole (CHM) and healthy co-twin, to ascertain the risks to the mother and baby of continuing the pregnancy, versus termination. 24 women with histologically confirmed CHM and healthy co-twin pregnancies decided to have a termination. 53 women continued with their pregnancies, though two had to have terminations because of severe pre-eclampsia, and 23 spontaneously aborted (<24 weeks' gestation). 28 pregnancies lasted 24 weeks or more, resulting in 20 livebirths. Chemotherapy to eliminate persistent gestational trophoblastic disease (pGTD) was required in three of 19 women (16%; 95% CI 3-39) who terminated their pregnancies in the first trimester, and in 12 of 58 (21%; 95% CI 11-33%) who continued their pregnancies. CHM and healthy co-twin pregnancies have a high risk of spontaneous abortion, but about 40% result in livebirths, without significantly increasing the risk of pGTD.