Matched-pair and propensity score comparisons of outcomes of patients with clinical stage I non-small cell lung cancer treated with resection or stereotactic radiosurgery.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an alternative to surgery for clinical stage I non-small cell lung cancer (NSCLC), but comparing its effectiveness is difficult because of differences in patient selection and staging. METHODS: Two databases were combined which contained patients treated from 1999 to 2008 by lobectomy (LR, n = 132), sublobar resection (SLR, n = 48), and SBRT (n = 137) after negative staging. Univariate and multivariate analysis were performed for survival (OS), total recurrence control (TRC comprises local-regional and distant control), and locoregional control (LRC) in our entire population. A matched-pair analysis was also performed that compared surgery and SBRT results. Median follow-up for the entire study population was 25.8 months. RESULTS: On univariate analysis, OS was significantly worse with SBRT and also correlated with histology, the Charlson comorbidity index, tumor size, and aspirin use; TRC correlated only with histology; and no variable significantly correlated with LRC. OS was significantly poorer for SBRT in the matched-pair analysis than for patients treated with surgery, but TRC and LRC were not significantly different between these groups. Multivariate analyses including propensity score as a covariate (controlling for all factors affecting treatment selection) found that OS correlated only with Charlson comorbidity index, and TRC correlated only with tumor grade. LRC correlated only with tumor size with or without propensity score correction. CONCLUSIONS: This retrospective study has demonstrated similar OS, LRC, and TRC with SBRT or surgery after controlling for prognostic and patient selection factors. Randomized clinical trials are needed to better compare the effectiveness of these treatments.

Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study.

BACKGROUND: MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease. METHODS: This phase 1-2 study was undertaken in five US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The final daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT00510718. FINDINGS: We noted antitumour effects at all doses, including decreases in serum prostate-specific antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased (18)F-fluoro-5alpha-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20-100%). The median time to progression was 47 weeks (95% CI 34-not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3-4 adverse event was dose-dependent fatigue (16 [11%] patients), which generally resolved after dose reduction. INTERPRETATION: We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1-2 trial validate in man preclinical studies implicating sustained androgen-receptor signalling as a driver in this disease. FUNDING: Medivation, the Prostate Cancer Foundation, National Cancer Institute, the Howard Hughes Medical Institute, Doris Duke Charitable Foundation, and Department of Defense Prostate Cancer Clinical Trials Consortium.

Case report: pelvic congestion syndrome as an unusual etiology for chronic hip pain in 2 active, middle-age women.

CONTEXT: The past 2 decades have shown a dramatic increase in the number of pelvic and hip injuries in female athletes. Accurate diagnosis of hip pain in active women has proven to be a challenge, as there is an extensive differential including both musculoskeletal and visceral problems. While the incidence of pelvic congestion syndrome (PCS) is not known, this condition may manifest as chronic hip pain in this patient population. EVIDENCE ACQUISITION: A PubMed search was undertaken for articles published in English from 1980 to 2012. Additional references were accrued from reference lists of research articles. STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 3. RESULTS: Diagnosis was established using magnetic resonance imaging. Both women were evaluated and treated by interventional radiology with gonadal vein embolization. Initial evaluation and subsequent follow-up was completed in the Sports Medicine Clinic to monitor chronic hip pain symptoms. Both patients experienced significant alleviation of chronic hip pain symptoms within several months after gonadal vein embolization, allowing for a return to the previous level of activity. CONCLUSION: Although PCS most commonly presents as pelvic pain, it is important to consider this condition in athletes with persistent hip pain. PCS may also present with the primary symptom of hip pain as in the 2 case reports described. With more awareness of this condition and appropriate diagnosis, PCS as an unusual etiology of chronic hip pain may be effectively treated with gonadal vein embolization.