Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials

<p>Abstract</p> <p>Background</p> <p>Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.</p> <p>Methods/design</p> <p>We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.</p> <p>Discussion</p> <p>Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.</p

Is hypofractionated reirradiation effective after symptomatic local recurrence in non-small cell lung cancer?

Purpose: To evaluate retrospectively the treatment results of recurrent non-small cell lung cancer (NSCLC) patients treated with second-line hypofractionated radiotherapy. Patients and methods: Twenty-five patients with locally advanced NSCLC and symptomatic local recurrence after primary hypofractionated radiotherapy, were retreated with second-line hypofractionated irradiation between July 1991 and April 1999. Maximum effort was undertaken to protect normal lung tissue with careful simulations, limited safety margins and customized blocking. The spinal cord was excluded with parallelly opposed isocentric oblique fields in central tumors. Total doses ranging between 2000-3000 cGy (median 2500 cGy) were delivered in 5-15 fractions. Nine patients were administered systemic chemotherapy (CT) before reirradiation. Survival analysis and subjective response rates were evaluated according to starting dates of both radiotherapy courses and clinical improvement in symptomatology, respectively. Results: Median follow-up time was 48 weeks (range 13-121 weeks). The mean time-interval between the two radiotherapy courses was 32 weeks (range 4-65 weeks). Overall improvement in symptomatology was found to be 72.7% (32 out of 44 patients), with a complete response rate of 38.6% (17 out of 44 patients). Hemoptysis was the best palliated symptom. Overall and post-reirradiation median survival times were found to be 48 and 17 weeks, respectively. The majority of patients were regularly followed-up until death. No Radiation Therapy Oncology Group (RTOG) toxicity grades III-IV were registered. Conclusion: Even though this is a retrospective study containing a small number of patients, hypofractionated reirradiation appears to be safe and effective in palliating symptoms related to NSCLC and prolonged survival can be offered

Prognostic factors in limited-stage small cell lung cancer of patients treated with combined modality approach.

Purpose: To evaluate the combined modality treatment results of patients with limited-stage small cell lung cancer (SCLC), who were treated and followed by the DE LCSG. Patients and methods: Sixty-three patients with limited-stage SCLC diagnosed between April 1991 and December 2002 were included. All patients were treated with combined chemotherapy and thoracic radiotherapy. Median age was 59 years (range 36-84), and all patients were male except 4. Surgery was performed for diagnosis in 3 patients. Four cycles of chemotherapy (median) were administered, composed of cisplatin-etoposide (CE) (26 patients), cyclophosphamide-vincristine-adriamycin (CAV) (10 patients) or alternated CE and CAV (18 patients). Nine patients received various chemotherapy regimes other than CE and/or CAV. A total dose of 5000 cGy with 180-200 cGy daily fractions was given to the primary tumor and mediastinum, excluding the spinal cord after 4500 cGy. Prophylactic cranial irradiation (PCI) was performed in 13 (20%) patients. Overall survival (OS) and progression-free survival (PFS) were calculated, beginning from the date of diagnosis and the end of radiotherapy, respectively. Kaplan-Meier method was used for obtaining survival rates. Log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. Results: Median follow-up time was 17 months (range 3-131). Median PFS and OS were 12 (range 1-131) and 17 (range 3-131) months, respectively. Two-year PFS and OS rates were 27% and 38%, respectively. During follow-up, 27 (43%) patients developed brain metastasis; among them only 3 had received PCI. Univariate analysis showed that addition of PCI significantly improved PFS (p=0.025) and advanced age was a favorable prognostic factor for OS (p=0.039). In the multivariate analysis, advanced age (p=0.034) and addition of PCI (p=0.004) were independent factors increasing PFS, however no significant prognostic factor influencing OS was found. Conclusion: Our treatment results are in accordance with the relevant literature. It is also concluded that PCI should be given to all patients with complete response to chemotherapy. However analysis of prognostic factors should be cautiously evaluated because of small number and heterogeneous distribution of patients in subgroups. Prospective studies are necessary for better determination of prognostic factors. © 2006 Zerbinis Medical Publications

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies : an individual participant data meta-analysis

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding