Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53

We report a 26-year-old female patient who was diagnosed within 4years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutation

Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Déclenchement artificiel du travail par les PGE1 (misoprostol)

La maturation du col et l'induction du travail concernent environ 20% des accouchements dont les deux tiers sont motivés par une indication médicale. Parmi les méthodes de déclenchement, les moyens médicamenteux, associés à l'amniotomie, sont les plus utilisés. Depuis 1992, la littérature s'enrichit régulièrement de publications sur l'utilisation d'un analogue de la prostaglandine E, le misoprostol (Cytotec®), dans le déclenchement du travail à terme. Son coût très modeste et son efficacité ont poussé les obstétriciens à utiliser ses effets sur la maturation cervicale et l'induction du travail. Le devenir néonatal et la morbidité maternelle sont équivalents quel que soit le type de prostaglandines utilisées. La dose optimale semble être de 50 g administrés toutes les quatre heures par voie vaginale

Influence of misoprostol or prostaglandin E(2) for induction of labor on the incidence of pathological CTG tracing: a randomized trial.

OBJECTIVE: To compare the efficacy and safety of misoprostol (prostaglandin E(1) (PGE(1))) with dinoprostone (prostaglandin E(2) (PGE(2))) for third trimester cervical ripening and labor induction. STUDY DESIGN: Patients requiring induction of labor were randomly assigned to receive either 50 microg of intravaginal misoprostol every 4 h or 0.5 mg of intracervical dinoprostone gel every 6 h. Eligibility criteria included gestation = 36 weeks. Primary outcome was the time interval from induction to delivery; secondary outcomes were mode of delivery, perinatal outcome, and interpretation of cardiotocogram (CTG) records. RESULTS: Two hundred women were randomly enrolled to receive either misoprostol (n = 100) or dinoprostone (n = 100). Time induction-to-delivery at 12, 24 and 48 h and the need for oxytocin were reduced with misoprostol (P < 0.05). Pathological CTG tracing according to FIGO and Melchior scores were more frequent in the misoprostol-treated group (P < 0.001). CONCLUSION: Misoprostol shortened the induction-to-delivery interval, but is associated with a higher incidence of abnormal CTG than prostaglandin E(2)

Effect of grade on disease-free survival and overall survival in FIGO Stage I adenocarcinoma of the endometrium.

Abstract Objective : To analyse the effect of differentiation on disease-free survival (DFS) and overall survival (OS) in patients with stage I adenocarcinoma of the endometrium. Patients and methods : From 1979 to 1995, 350 patients with FIGO stage IA–IC with well (G1), moderately (G2) or poorly (G3) differentiated tumors were treated with surgery and high dose-rate brachytherapy with or without external radiation. Median age was 65 years (39–86 years). Results : The 5-year DFS was 8863% for the G1 tumors, 7764% for the G2 tumors, and 6767% for the G3 tumors (P50.0049). With regard to the events contributing to DFS, the 5-year cumulative percentage of local relapse was 4.6% for the G1 tumors, 9.0% for the G2 tumors, and 4.6% (P50.027) for the G3 tumors. Cumulative percentage of metastasis was 1.4, 6.3 and 7.2% (P,0.001), respectively, whereas percentages of death were 6.0, 7.9 and 20.7% (P,0.001). The 5-year OS was 9163, 8364 and 7667%, respectively (P50.0018). In terms of multivariate hazard ratios (HR), the relative differences between the three differentiation groups correspond to an increase of 77% of the risk of occurrence of either of the three events considered for the DFS (HR51.77, 95% Cl [0.94–3.33]), (P50.078) for the G2 tumors and of 163% (HR52.63, 95% Cl [1.27–5.43]), (P50.009) for the G3 tumors with respect to the G1 tumors. The estimated relative hazards for OS are, respectively, in line with those for DFS: HR51.51 (P50.282) for the G2 tumors; and HR53.37 (P50.003) for the G3 tumors. Conclusion : Patients with grade 1 tumors are those least exposed to either local relapse, metastasis, or death. In contrast patients with grade 2 tumors seem to be at higher risk of metastasis, whereas patients with grade 3 tumors appear at higher risk of death. Since we have looked at the first of three competing events (local relapse, metastasis and death), this suggests that patients with grade 3 tumors probably progress to death so fast that local relapse, if any, cannot be observed. Ó 2000 Elsevier Science Ireland Ltd. All rights reserved

Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53.

We report a 26-year-old female patient who was diagnosed within 4 years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18 months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations