ABSTRACT
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Gestational Trophoblastic Disease , Pregnancy , Female , Humans , Retrospective Studies , Gestational Trophoblastic Disease/drug therapy , Nomograms , Risk FactorsABSTRACT
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.
Subject(s)
Gestational Trophoblastic Disease , Pregnancy , Female , Humans , Gestational Trophoblastic Disease/drug therapy , Retrospective Studies , Models, StatisticalABSTRACT
BACKGROUND: Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse. METHODS: Between January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5-6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR. RESULTS: In LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5-6 patients. The incidence of MTX toxicity was not influenced by BSA or weight. CONCLUSIONS: In the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Gestational Trophoblastic Disease , Pregnancy , Female , Humans , Methotrexate , Leucovorin , Body Surface Area , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Gestational Trophoblastic Disease/drug therapy , DactinomycinABSTRACT
Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are the rarest subtypes of gestational trophoblastic disease (GTD). Their diagnosis is complicated and lacks specific and sensitive tumour markers. They are slow-growing tumours and can occur months to years after any type of antecedent pregnancy. The primary treatment for localised disease is hysterectomy. However, extra-uterine invasion and/or metastasis occur in about one-third of cases and still cause death in a small number. Most patients are young; hence, fertility preservation is a consideration. The major obstacle for prognosis is chemotherapy resistance. The current understanding of these tumours remains elusive and no randomized controlled trials have been done. Even those centres treating a large number of patients with GTD will infrequently manage PSTT/ETT. In this review, we assess progress in the understanding of the disease and discuss four main clinical challenges - establishing conformity of practice, devising a risk-adapted approach to clinical management, establishing long-term follow-up data and evaluating therapies for poor prognosis and multi drug-resistant patients.
Subject(s)
Gestational Trophoblastic Disease , Trophoblastic Tumor, Placental Site , Uterine Neoplasms , Female , Gestational Trophoblastic Disease/drug therapy , Humans , Hysterectomy , Placenta , Pregnancy , Trophoblastic Tumor, Placental Site/diagnosis , Trophoblastic Tumor, Placental Site/surgery , Uterine Neoplasms/surgeryABSTRACT
BACKGROUND: The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear. METHODS: Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR). RESULTS: Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR. CONCLUSIONS: CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended.
Subject(s)
Gestational Trophoblastic Disease/pathology , Radiography, Thoracic/methods , Tomography, X-Ray Computed/methods , Female , Gestational Trophoblastic Disease/diagnostic imaging , Humans , Pregnancy , Prognosis , Risk FactorsABSTRACT
High-risk gestational trophoblastic neoplasia (GTN) is highly chemosensitive with an excellent prognosis with treatment. Historically in the United Kingdom, the high-risk regimens used have been M-EA (methotrexate, etoposide, dactinomycin) (Sheffield) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) (Charing Cross, London) with prior published data suggesting no difference in survival between these. Our Sheffield treatment policy changed in 2014, switching from M-EA to EMA-CO, aiming to reduce time in hospital, and harmonise UK practice. We aimed to report the toxicities, response rates and survival outcomes for 79 patients with high-risk GTN treated in the first-line setting with either M-EA (n = 59) or EMA-CO (n = 20) from 1998 to 2018. Median duration of treatment was similar (M-EA, 17.3 weeks (IQR 13.9-22.6) and 17.6 weeks (IQR 13.4-20.7) with EMA-CO. For M-EA, overall human chorionic gonadotrophin (hCG) complete response (CR) rate was 84.7% (n = 50/59). Two patients died of drug-resistant disease after several lines of multiagent chemotherapy; overall survival is 96.6% (median follow-up 10.4 years). For EMA-CO, overall hCG CR rate was 70%, overall survival is 100% (median follow-up 4 years). In our experience, patients treated with EMA-CO experienced an apparent increased incidence of neutropenia, non-neutropenic Grade 3-4 infection, peripheral neuropathy and more treatment delays and nights in hospital. Granulocyte-colony stimulating factor, after both EMA and CO arms, titrated to baseline neutrophil count improved the toxicity profile. Both treatment regimens are associated with excellent prognosis; selection of regimen may be further guided by individual patients' personal, social and family circumstances. There is further rationale to explore whether these regimens can be refined, such as 2-weekly EMA, to optimise patient experience and reduce toxicity while maintaining efficacy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gestational Trophoblastic Disease/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Dactinomycin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Methotrexate/administration & dosage , Pregnancy , Risk Factors , Vincristine/administration & dosageABSTRACT
BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.
Subject(s)
Trophoblastic Neoplasms/mortality , Trophoblastic Neoplasms/therapy , Trophoblastic Tumor, Placental Site/mortality , Trophoblastic Tumor, Placental Site/therapy , Uterine Neoplasms/mortality , Uterine Neoplasms/therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chorionic Gonadotropin/blood , Cohort Studies , Combined Modality Therapy , Databases, Factual , Female , Humans , Hysterectomy , Pregnancy , Prognosis , Retrospective Studies , Trophoblastic Neoplasms/blood , Trophoblastic Tumor, Placental Site/blood , United Kingdom/epidemiology , Uterine Neoplasms/bloodABSTRACT
Gestational trophoblastic disease is a rare complication of pregnancy that can develop into cancer. Medical outcomes of gestational trophoblastic disease are well researched, but the effect of the disease on health-related quality of life (HRQOL) requires attention if care is to be improved. This systematic review was designed to establish the effect of gestational trophoblastic disease and its treatment on HRQOL and to identify the appropriateness of HRQOL measures. Quantitative studies found HRQOL in long-term survivors of gestational trophoblastic disease to be at or above population norms. The disease had a negative effect on HRQOL for patients who experienced physical, psychological, and social sequelae related to the condition. Clinically significant levels of anxiety, depression, sexual dysfunction, and fertility-related distress were found in these patients. The results should be treated with caution because the evidence base was limited to small heterogeneous samples, data were retrospective, and a range of measures was used. Within qualitative studies on HRQOL for survivors of gestational trophoblastic disease, new conditions emerged, including nerve damage, fatigue, amenorrhoea, and grief. These areas are not captured in existing patient-reported outcome measures, and the content might not be valid for this population. Further qualitative research might lead to the development of a specific patient-reported outcome measure for gestational trophoblastic disease, providing reliable, meaningful, and valid assessments, and allowing longitudinal data to be obtained.
Subject(s)
Gestational Trophoblastic Disease/therapy , Patient Reported Outcome Measures , Quality of Life , Cost of Illness , Evidence-Based Medicine , Female , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/physiopathology , Gestational Trophoblastic Disease/psychology , Health Status , Humans , Mental Health , Predictive Value of Tests , Pregnancy , Risk Factors , Treatment OutcomeABSTRACT
PURPOSE/OBJECTIVES: To explore the experiences of women with gestational trophoblastic neoplasia during and after treatment to understand their perspectives, priorities, and concerns.â©. RESEARCH APPROACH: A descriptive, exploratory study using in-depth semistructured interviews.â©. SETTING: All interviews were conducted in a quiet, designated room at Weston Park Hospital in Sheffield, South Yorkshire.â©. 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.â©. 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.â©. 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.â©. 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.â©. 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.
Subject(s)
Antineoplastic Agents/therapeutic use , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Gestational Trophoblastic Disease/drug therapy , Patient Satisfaction/statistics & numerical data , Stem Cell Transplantation , Adult , England , Female , Humans , Middle Aged , Pregnancy , Qualitative ResearchABSTRACT
BACKGROUND: This is the second update of a Cochrane review that was first published in 2009, Issue 1, . Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. OBJECTIVES: To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials. SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model. MAIN RESULTS: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility. AUTHORS' CONCLUSIONS: Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.
Subject(s)
Antineoplastic Agents/administration & dosage , Dactinomycin/administration & dosage , Gestational Trophoblastic Disease/drug therapy , Methotrexate/administration & dosage , Antineoplastic Agents/adverse effects , Case-Control Studies , Cohort Studies , Dactinomycin/adverse effects , Drug Administration Schedule , Female , Humans , Leucovorin/administration & dosage , Methotrexate/adverse effects , Pregnancy , Randomized Controlled Trials as Topic , Risk , Vitamin B Complex/administration & dosageABSTRACT
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. OBJECTIVES: To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were included. DATA COLLECTION AND ANALYSIS: We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. MAIN RESULTS: The search identified no RCTs; therefore we were unable to perform any meta-analyses. AUTHORS' CONCLUSIONS: RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Subject(s)
Drug Resistance, Neoplasm , Gestational Trophoblastic Disease/drug therapy , Neoplasm Recurrence, Local/drug therapy , Female , Humans , PregnancyABSTRACT
OBJECTIVE: To review the outcome of patients treated for low-risk gestational trophoblastic neoplasia (GTN) over a 10-year period with the particular aim of assessing response to treatment in Stages I and III disease. Approximately 90% of women requiring treatment for GTN have low-risk disease. Methotrexate is the treat- ment of choice in the UK and achieves complete response rates of 50% and 90%. STUDY DESIGN: A retro- spective review of management and outcomes of patients treated for low-risk GTN at the Trophoblastic Disease Centre, Sheffield, UK, from 1997 to 2006. RESULTS: Overall 280 patients were treated for low- risk GTN during this time; 8.6% had stage III disease. Single-agent methotrexate was used as first-line therapy in 99% of cases, with a remission rate of 56%. There was no significant difference (p=0.67) in the complete response rate after first-line methotrexate between those with stage I and those with stage III disease. CONCLUSION: The overall cure rate for women with low-risk GTN was high (99.6%), and the complete response rate after first-line management was not sig- nificantly different between stages I and III disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Gestational Trophoblastic Disease , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dactinomycin/therapeutic use , Female , Humans , Methotrexate/therapeutic use , Pregnancy , Remission Induction , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of this study was to determine whether lesions found on computed tomography (CT) imaging of the thorax would affect FIGO (International Federation of Gynecology and Obstetrics) 2000 risk score and/or alter clinical management. METHODS: The Sheffield Trophoblastic Disease database was searched for all new patients registered for staging/scoring investigations between January 1, 2006, and June 30, 2010. The FIGO 2000 score was noted and then recalculated using information from CT scan reports. Where a change of risk score would have affected a patient's management, the case notes were further reviewed. RESULTS: 191 patients had undergone both modalities of imaging. Using standard FIGO scoring, 169 and 22 patients were noted to be at low and high risk, respectively. Using information from CT imaging, only a further 20 patients would have been reclassified as high risk. Fifteen of these "new" high-risk patients required salvage treatment with intravenous chemotherapy; all were cured. CONCLUSIONS: With no potential advantage in terms of patient outcome and significantly increased radiation dose, there is little justification for routine CT imaging of the thorax in the initial assessment of new patients with gestational trophoblastic neoplasia.
Subject(s)
Gestational Trophoblastic Disease/diagnostic imaging , Gestational Trophoblastic Disease/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Radiography, Thoracic , Tomography, X-Ray Computed , Administration, Intravenous , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chorionic Gonadotropin/blood , Dactinomycin/administration & dosage , Etoposide/administration & dosage , Female , Gestational Trophoblastic Disease/drug therapy , Humans , Lung Neoplasms/drug therapy , Methotrexate/administration & dosage , Neoplasm Staging , Pregnancy , Risk Assessment , Salvage TherapyABSTRACT
BACKGROUND: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited. METHODS: Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided. RESULTS: During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided. CONCLUSIONS: Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Menopause, Premature , Ovary/radiation effects , Adolescent , Adult , Antineoplastic Agents, Alkylating/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Carmustine/administration & dosage , Carmustine/adverse effects , Child , Child, Preschool , Cytarabine/administration & dosage , Cytarabine/adverse effects , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , England/epidemiology , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Follow-Up Studies , Humans , Infant , Melphalan/administration & dosage , Melphalan/adverse effects , Poisson Distribution , Proportional Hazards Models , Radiotherapy Dosage , Risk Assessment , Surveys and Questionnaires , Vinblastine/administration & dosage , Vinblastine/adverse effects , Wales/epidemiology , Young AdultABSTRACT
OBJECTIVE: To describe the evolution of a highly regarded and unique model of multidisciplinary care providing support, monitoring, and treatment for all gestational trophoblastic disease (GTD) patients referred to Sheffield Trophoblastic Disease Centre, 1 of the 3 United Kingdom (UK) supraregional GTD centers. BACKGROUND: The UK GTD service was first established in 1973 and since its inception has centralized care for GTD patients and played a leading international role in developing therapies, management protocols, and biomarker assays with good outcomes for patients. The service preceded recent trends towards centralization for rare cancers in the U.K. In Sheffield the GTD team has evolved to become a true multidisciplinary team with a strong nursing component, which is set to expand in the future. RESULTS: Centralization of care for GTD in the U.K. has been directly associated with the impressive results the service has achieved, with high cure rates (98-100%) and low (5-8%) chemotherapy rates. The addition of GTD nurse specialists has been beneficial to patients as they provide a communication link between patients and their clinicians and ensure that information, support, and advice is available for all GTD patients, both in hospital and at home. CONCLUSION: The UK GTD service is an internationally renowned, multidisciplinary organization. The service achieves impressive clinical results and now features a strong nursing component. The addition of nurse specialists has enabled the team to offer both clinical and psychological care and means that specialist advice is available for patients and healthcare professionals involved in giving care to this patient group.
Subject(s)
Gestational Trophoblastic Disease/therapy , Nurse Clinicians , Female , General Practice , Gynecology , Humans , Medical Oncology , Patient Care Team , Pregnancy , Specialization , Treatment Outcome , United KingdomABSTRACT
OBJECTIVE: To present survival rates of high-risk gestational trophoblastic neoplasia (GTN) (FIGO score > 7) patients treated between 1995 and 2010 in the U.K. Death due to GTN is largely confined to patients with high-risk disease. In the U.K. a national system ensures that all patients are treated at only 2 specialist centers: Charing Cross Hospital (CXH) in London and Weston Park Hospital (WPH) in Sheffield. STUDY DESIGN: A total of 196 high-risk patients were identified using the CXH and WPH GTN databases, based on the risk score at the time of presentation. RESULTS: In all, 140 CXH and 56 WPH high-risk patients were treated with EMA/CO (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine) and MEA (methotrexate, etoposide, actinomycin D), respectively. The FIGO score at presentation ranged from 6-23. Eight patients (7from WPH and 1 from CXH) who were treated prior to 2002 as high-risk based on their pre-2002 scoring scored a 6 using FIGO 2002. Two (1%) patients died within 4 weeks of starting treatment (early death), 12 (6%) relapsed, and 9 patients subsequently died due to drug resistance. The overall survival was 94%, with a median follow-up of 4.69 years. CONCLUSION: In the context of a national trophoblastic disease service, patients with high-risk GTN have an excellent prognosis with EMA/CO or MEA.
Subject(s)
Gestational Trophoblastic Disease/drug therapy , Gestational Trophoblastic Disease/mortality , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chorionic Gonadotropin/blood , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Dactinomycin/administration & dosage , Dactinomycin/therapeutic use , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Etoposide/therapeutic use , Female , Gestational Trophoblastic Disease/pathology , Hospitals, Special , Humans , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Neoplasm Recurrence, Local , Neoplasm Staging , Pregnancy , Prognosis , Risk Factors , Survival Rate , Treatment Outcome , United Kingdom , Vincristine/administration & dosage , Vincristine/therapeutic useABSTRACT
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. OBJECTIVES: To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were included. DATA COLLECTION AND ANALYSIS: We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. MAIN RESULTS: The search identified no RCTs; therefore we were unable to perform any meta-analyses. AUTHORS' CONCLUSIONS: RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Subject(s)
Drug Resistance, Neoplasm , Gestational Trophoblastic Disease/drug therapy , Neoplasm Recurrence, Local/drug therapy , Female , Humans , PregnancyABSTRACT
Lymphomas are solid tumours of the immune system. Hodgkin's lymphoma accounts for about 10% of all lymphomas, and the remaining 90% are referred to as non-Hodgkin lymphoma. Non-Hodgkin lymphomas have a wide range of histological appearances and clinical features at presentation, which can make diagnosis difficult. Lymphomas are not rare, and most physicians, irrespective of their specialty, will probably have come across a patient with lymphoma. Timely diagnosis is important because effective, and often curative, therapies are available for many subtypes. In this Seminar we discuss advances in the understanding of the biology of these malignancies and new, available treatments.
Subject(s)
Lymphoma, Non-Hodgkin/diagnosis , Antineoplastic Agents/therapeutic use , Humans , Lymphoma, Non-Hodgkin/classification , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/epidemiology , Neoplasm Staging , PrognosisABSTRACT
OBJECTIVE: To compare the initial clinical presentation of patients who were treated at our center for gestational trophoblastic neoplasia (GTN) between 1996 and 1998 and between 2006 and 2008. STUDY DESIGN: All patients seen at Weston Park Hospitalfor GTN (excluding placental site trophoblastic tumor [PSTT]) between 1996 and 1998 (total, 79) and between 2006 and 2008 (total, 139) were identified and their medical records reviewed. Features from when they first presented with gestational trophoblastic disease (GTD), excluding PSTT, were recorded. During those time periods 1,391 and 1,623 patients, respectively, were registered at our center with GTD. RESULTS: The following results were noted: abnormal vaginal bleeding remains the most common presentation; the proportion of abnormal ultrasound scans at initial diagnosis has risen from 1% to 12%; the mean gestational age of the antecedent pregnancy has dropped from 11.3 to 10.1 weeks; the mean number of evacuations has fallen from 1.9 to 1.2, and the proportion of patients having 2 evacuations has more than halved; and the proportion of patients presenting with GTD requiring chemotherapy for GTN was 4.2% (59 of 1,391) for 1996-1998 and 6.7% (109 of 1,623) for 2006-2008. CONCLUSION: An improvement in ultrasound technology and expertise in early pregnancy is likely to have contributed to a trend toward a lower gestational age at diagnosis of GTD. We noted a major shift in practice towards a higher threshold for repeat evacuations and an increased proportion of patients with GTN receiving chemotherapy.
Subject(s)
Gestational Trophoblastic Disease/diagnosis , Uterine Neoplasms/diagnosis , Antineoplastic Agents/therapeutic use , Female , Gestational Age , Gestational Trophoblastic Disease/therapy , Humans , Pregnancy , Retrospective Studies , Ultrasonography , Uterine Hemorrhage/etiology , Uterine Neoplasms/therapy , Uterus/diagnostic imaging , Vacuum Curettage/statistics & numerical data , Vacuum Curettage/trendsABSTRACT
OBJECTIVE: To review retrospectively the causes of death in unselected patients with gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Between 1975 and 2010, 905 patients with GTN were treated at the Sheffield Centre. Twenty-four of them died. The medical records of these patients were reviewed. RESULTS: Of the 24 patients, 11 died during initial treatment. A further 8 died from disease relapse and progression of the disease. The cause of death was unrelated in the other 5, who were excluded from analysis. For the remaining 19 patients, death was due to metastatic tumor in 13 and was treatment related in 6. Adverse prognostic features for death from GTN included histology (7 were placental site trophoblastic tumor [PSTT]), risk score (15 were high risk) and chemotherapy resistance. All 5 of the patients who died of acute treatment-related complications (invariably sepsis and/or multiorgan failure) still had active GTN at the time of death; all were treated prior to 1987. One multitreated patient died of acute myeloid leukemia 3 years posttreatment. CONCLUSION: Metastatic multidrug-resistant PSTT was and still is the single most important cause of death. Death from choriocarcinoma was with nonpulmonary metastases not responding to initial treatment. Early treatment-related death (from sepsis) is nowadays avoidable.