John Tidy

Presentation and management of choriocarcinoma after nonmolar pregnancy

Objective To ascertain the mode of presentation and treatment outcome for women with choriocarcinoma after a nonmolar pregnancy.

First line chemotherapy in low risk gestational trophoblastic neoplasia

BACKGROUNDnThis 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.nnnOBJECTIVESnTo determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.nnnSEARCH METHODSnWe 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.nnnSELECTION CRITERIAnFor 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.nnnDATA COLLECTION AND ANALYSISnTwo 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.nnnMAIN RESULTSnWe 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.nnnAUTHORS CONCLUSIONSnActinomycin 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.

Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

BACKGROUNDnGestational 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.nnnOBJECTIVESnTo determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic.nnnSEARCH METHODSnWe 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.nnnSELECTION CRITERIAnOnly randomised controlled trials (RCTs) were included.nnnDATA COLLECTION AND ANALYSISnWe designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses.nnnMAIN RESULTSnThe search identified no RCTs; therefore we were unable to perform any meta-analyses.nnnAUTHORS CONCLUSIONSnRCTs 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.

Impact of the revised FIGO/WHO system on the management of patients with gestational trophoblastic neoplasia

OBJECTIVEnTo study the effect of a change in disease scoring systems on the management of patients with gestational trophoblastic neoplasia (GTN) in our supra-regional treatment centre.nnnMETHODSnWe reviewed disease characteristics and treatment outcomes in 632 GTN patients managed at our centre from 1973 to 2006. Two disease scoring systems were used sequentially, the Sheffield modification of the Charing Cross Scoring System (SCCSS) before 2000, and the revised FIGO/modified WHO system (FIGO 2000) thereafter.nnnRESULTSnUsing the SCCSS 573 (90.7%) patients were classified as low risk (LR) and 59 (9.3%) as high risk (HR). With FIGO 2000, 587 (92.9%) were LR and 45 (7.1%) HR. For LR patients, the complete response (CR) to first line single agent chemotherapy was 77% before 2000 and 61.6% from 2000 to 2006. For HR patients, the CR rates with first line chemotherapy were 79.5% and 75% respectively. The higher threshold for assigning a patient as HR using FIGO 2000 had an impact on the success of treatment; only 7/19 patients (37%) who were scored 6 by FIGO 2000, and thus treated as LR with methotrexate/folinic acid, achieved a CR.nnnCONCLUSIONnIn our experience, the revised FIGO/modified WHO scoring system has down scored some patients who would have been considered as high risk with the previous scoring system. A trend to lower CR with first line chemotherapy and an increase in the need for second line chemotherapy was seen.

A retrospective study to evaluate single agent methotrexate treatment in low risk gestational choriocarcinoma in the United Kingdom

OBJECTIVEnTo determine whether single agent chemotherapy with intramuscular methotrexate 50mg administered on days 1, 3, 5, and 7 and oral folinic acid 15mg administered on days 2, 4, 6, and 8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma.nnnMETHODnElectronic databases were searched to identify patients with gestational choriocarcinoma at the Sheffield and Charing Cross supra-regional trophoblastic disease centres from January 2000 to December 2011. Clinical notes of low risk patients with FIGO score 0-6 were retrospectively reviewed to assess treatment outcomes and subsequent relapse.nnnRESULTSn65 patients were identified with low risk choriocarcinoma. Serum hCG levels normalised in 24 patients without the requirement of chemotherapy (19 with histological confirmation, 4 highly suspicious histology and 1 clinical diagnosis). Of 23 patients with histologically confirmed choriocarcinoma, 8 (35%) had a sustained complete response to IM MTX/FA and did not relapse. Both patients with FIGO score 6, and 1 patient with FIGO stage III metastatic disease developed resistance to IM MTX/FA and required further treatment. Despite the development of drug resistance or relapse all patients were successfully salvaged by subsequent treatments.nnnCONCLUSIONSnNot all patients with low risk choriocarcinoma that have had primary intervention prior to staging, such as surgical resection or uterine evacuation will require chemotherapy, providing hCG levels continue to decline to normal. Low risk (FIGO 0-5) patients should initially receive IM MTX/FA due to its low toxicity, outpatient administration and reasonable efficacy. Patients with FIGO score 6 or FIGO stage III disease should make an informed choice between IM MTX/FA and combination chemotherapy.

The multidisciplinary colposcopy meeting: recommendations for future service provision and an analysis of clinical decision making

Please cite this paper as: Palmer J, Wales K, Ellis K, Dudding N, Smith J, Tidy J. The multidisciplinary colposcopy meeting: recommendations for future service provision and an analysis of clinical decision making. BJOG 2010;117:1060–1066.

Understanding the impact of the treatment pathway upon the health-related quality of life of women with newly diagnosed endometrial cancer – A qualitative study

PURPOSEn(1) To determine the impact of treatment and recovery on the health-related quality of life (HRQoL) of endometrial cancer (EC) patients. (2) To explore how treatment types and delivery affect HRQoL and invite suggestions for improvement.nnnMETHODSnQualitative study. In-depth, semi-structured interviews at 3, 6, 9 or 12 months post-treatment were carried out with 22 women with stage IA to IVB EC who had undergone treatment at a tertiary referral centre for gynaecological cancers in Sheffield, UK. 21 were treated surgically and 4 received adjuvant treatment. Data were analysed using an inductive thematic approach.nnnRESULTSnFour dominant themes emerged regarding the treatment pathway: pre-treatment concerns, experience during treatment, post-treatment and survivorship issues. Expectations and understandings of EC and its treatment were often inaccurate. Proper explanations eased anxiety but were uncommon. Laparoscopic surgery was welcomed where offered but did not necessarily influence coping ability. Instead, women evaluated treatment impacts against their expectations. Treatments affected womens physical abilities, self-perception and relationships resulting in re-evaluation of lifestyle.nnnCONCLUSIONSnThe impact of treatment upon HRQoL for women with EC differs from other gynaecological cancers. Better information provision would enhance coping ability. Coping methods and expectations appear to influence HRQoL more than treatment modality.

Predicting gestational trophoblastic neoplasia (GTN): Is urine hCG the answer?

BACKGROUNDnPrevious studies on the significance of hCG to predict gestational trophoblastic neoplasia (GTN) have been too small for robust conclusions to be reached. Our aim in this study was to analyse the significance of urine hCG in predicting GTN in a large population.nnnMETHODSnDetails of 3926 patients were available for analysis. Information regarding age, dates of diagnosis and registration, urine hCG levels, antecedent pregnancy and chemotherapy were prospectively collected and used for analyses. Patients were stratified into different groups according to urine hCG level (IU/L); < 50, 50-99, 100-249, 250-499, 500-999, 1000-9999 and ≥10,000. Multivariate analyses were used to identify the prognostic indicators of GTN.nnnRESULTSnUrine hCG and antecedent pregnancy were the most powerful indicators for developing GTN (P<0.01). None of the patients with partial mole and urine hCG <50 IU/L (Normal level=40 IU/L) developed GTN. The risk of GTN was >35% in all patients with urine hCG ≥500 IU/L. GTN developed in 70% of patients with complete mole and urine hCG ≥10,000 IU/L.nnnCONCLUSIONnUrine hCG is sensitive test for GTN. Urine hCG level is a powerful prognostic indicator for the GTN. Patients with partial mole could be safely discharged from the surveillance programme once their hCG have normalised. Patients with urine hCG ≥249 IU/L, whether partial or complete molar pregnancy, appear to benefit from intensive surveillance. Prophylactic chemotherapy could be considered when there are problems with surveillance.

Management of microinvasive cervical cancer: a British Society for Colposcopy and Cervical Pathology audit.

The incidence of microinvasive cervical cancers seems to be increasing as a result of screening. However, there is little national or international guidance on best management or follow-up of women treated with conservation of the cervix. Objective The study aimed to assess the current management and follow-up of women with stage IA cervical cancer, according to the International Federation of Gynecology and Obstetrics, within the United Kingdom. Design/Setting This study is a multicenter national audit of a clinical practice in the United Kingdom. Materials and Methods A structured questionnaire was sent and returned electronically to all lead colposcopists in the United Kingdom on the management and follow-up of women with stage IA cervical cancer according to the International Federation of Gynecology and Obstetrics. The study was approved by the British Society for Colposcopy and Cervical Pathology. Results Of the 210 lead colposcopists, 110 (52%) responded. All reported that women with stage IA cervical cancer are discussed at a gynecologic multidisciplinary team meeting. Women who managed conservatively with their cervix in situ are followed up for at least 5 years. There is a wide variation in clinical management of cases with lymphovascular space involvement (LVSI) and depth of invasion greater than 3 mm (stage IA2). Conclusions The pattern and practice of follow-up for stage IA cervical cancer is highly variable. The development of national guidance should be considered.

The outcome for women with microinvasive cervical cancer with stromal invasion 1 mm or less: should we always re-excise?

To assess the management and outcome for women with microinvasive cervical cancer with stromal invasion 1 mm or less, examining the impact of re-excision. A retrospective cohort study with interval analysis performed between December 2000 and December 2010. Sheffield Gynaecological Cancer Centre and Jessop Wing Colposcopy Unit, Sheffield, UK. Women diagnosed with microinvasive cervical cancer with stromal invasion 1 mm or less during the allocated study period. Methods used is a retrospective cohort study. Risk of recurrence and mortality from disease; incidence of residual disease in repeat excision specimens. A total of 140 women were identified as having microinvasive cervical cancer with stromal invasion 1 mm or less. Sixty-three (45%) had a completely excised lesion; 77 (55%) had an incompletely excised lesion at first treatment. Fifty-five women underwent repeat excision. No residual disease was found in the majority (n=40; 73%). No women suffered disease recurrence or died from disease during the allocated study period. Outcome for women with microinvasive cervical cancer with stromal invasion 1 mm or less is excellent. Repeat excision is associated with very low rates of residual disease. A more conservative approach to follow-up incorporating HPV testing should be explored.