Efficacy and tolerance of salvage radiotherapy after radical prostatectomy, with emphasis on high-risk patients suited for adjuvant radiotherapy

Background and purpose

Goals of this study are to report the outcomes and tolerance of salvage radiotherapy (SRT) after prostatectomy, to identify risk factors for failure after SRT and to evaluate how these results compare with published results of immediate post-operative adjuvant radiotherapy (ART).

Material and methods

Men receiving SRT for elevated PSA levels after radical prostatectomy (RP) were included. Biochemical progression-free survival (bPFS), overall survival (OS) and disease-specific survival (DSS) were estimated. Risk factors for biochemical failure and death were evaluated. Late toxicity and quality of life were evaluated. Secondary bPFS (defined as bPFS from prostatectomy until progression after radiotherapy) was calculated for high-risk patients (pT3 and/or positive surgical margins) in order to compare SRT outcomes with ART.

Results

197 Men were included. Five-year bPFS after SRT was 59% (95% CI 49-69%). Five-year OS and DSS were 90% (85-96%) and 97% (93-100%), respectively. Capsular perforation (pT ? T3), negative surgical margins and serum PSA > 1 ng/ml at the start of RT were significant predictors of lower bPFS. Patients without any negative factors had a 5-year bPFS of 89%. No severe late toxicity was reported. Five-year secondary bPFS for SRT in high-risk patients was 78% and comparable with published results for ART.

Conclusions

Salvage radiotherapy for patients with organ-confined prostate cancer was effective and well tolerated. SRT outcomes were comparable with published ART results for high-risk patients. Initially monitoring serum PSA and considering early SRT for these patients are not harmful and might be a valuable alternative for immediate ART.     

C7orf10 encodes succinate-hydroxymethylglutarate CoA-transferase, the enzyme that converts glutarate to glutaryl-CoA

Glutarate, a side-product in the metabolism of tryptophan and lysine, is metabolized by conversion to glutaryl-CoA by a transferase using succinyl-CoA as a coenzyme donor. The enzyme catalyzing this conversion has not been formally identified. However, a benign form of glutaric aciduria (glutaric aciduria type III) is due to mutations in C7orf10, a putative member of the coenzyme A transferase class III family. In the present work, we show that recombinant human C7orf10 catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. C7orf10 could use many dicarboxylic acids as CoA acceptors, the best ones being glutarate, succinate, adipate, and 3-hydroxymethylglutarate. Confocal microscopy analysis of CHO cells transfected with a C7orf10-GFP fusion protein indicated that C7orf10 is a mitochondrial protein, in agreement with the presence of a predicted mitochondrial propeptide at its N-terminus. The effect of a missense mutation (p.Arg336Trp) found in the homozygous state in several patients with glutaric aciduria type III and present in the general population at a low frequency was also investigated. The p.Arg336Trp mutation led to the production of insoluble and inactive C7orf10 both in Escherichia coli and in HEK293T cells. These findings indicate that C7orf10 is implicated in the metabolism of glutarate, but possibly also of longer dicarboxylic acids. Homologues of this enzyme are found in numerous bacterial operons comprising also a putative glutaryl-CoA dehydrogenase, indicating that an enzyme with similar specificity exists in prokaryotes.     

Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2-3 diffuse large B-cell lymphoma.

BACKGROUND: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite of numerous reports on immune system-lymphoma interactions. This study addresses the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL. PATIENTS AND METHODS: Absolute values of blood lymphocyte subsets and monocytes were prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at diagnosis and aaIPI were evaluated with regard to clinical outcome. RESULTS: Low median cell counts of 337, 211, and 104/mul were evidenced for the CD4+, CD8+ T, and natural killer (NK) cells, respectively. In univariate analysis, only NK cell count [odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001] and aaIPI [OR = 2.29 (0.95, 5.45), P = 0.06] were associated with induction treatment response. Low NK cell count [Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01] and aaIPI 3 [HR = 1.95 (1.20, 3.16), P = 0.01] were also associated with a shorter event free survival (EFS). In multivariate analysis, NK cell count was associated with response [OR = 1.77 (1.24, 2.54), P = 0.002] and EFS [HR = 1.25 (1.04, 1.50) P = 0.02] independently of aaIPI. CONCLUSIONS: This study shows an association between circulating NK cell number and clinical outcome in DLBCL, possibly important in the context of the broadening use of rituximab, a likely NK-dependent therapy.     

Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT.

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction.     

Enamel reduction procedures in orthodontic treatment

Various combinations of enamel reduction procedures can be used to create space between teeth, to correct discrepancies between mandibular and maxillary teeth and to correct morphologic anomalies during orthodontic treatment. In particular, acid-enhanced interproximal enamel reduction significantly reduces surface roughness. This article presents a review of the literature on enamel reduction procedures.     

Temporary atrial epicardial pacing as prophylaxis against atrial fibrillation after heart surgery: a meta-analysis

INTRODUCTION: Recent studies have reported the use of temporary epicardial atrial pacing as prophylaxis for postoperative atrial fibrillation (AF). The aim of this study was to assess the effect of pacing therapies for prevention of postoperative AF using meta-analysis. METHODS AND RESULTS: Using a computerized MEDLINE search, eight pacing prophylaxis trials with 776 patients were included in the meta-analysis. Trials compared control patients to patients randomized to right atrial, left atrial, or biatrial pacing used in conjunction with either fixed high-rate pacing or overdrive pacing. Overdrive biatrial pacing (OR 2.6, CI 1.4-4.8), overdrive right atrial pacing (OR 1.8, CI 1.1-2.7), and fixed high-rate biatrial pacing (OR 2.5, CI 1.3-5.1) demonstrated a significant antiarrhythmic effect for prevention of AF after open heart surgery. Furthermore, studies investigating overdrive left atrial pacing and fixed high-rate right atrial pacing have been underpowered to assess efficacy. CONCLUSION: Biatrial overdrive and fixed high-rate pacing and right atrial fixed high-rate pacing reduced the risk of new-onset AF after open heart surgery, and the relative risk reduction is approximately 2.5-fold. These results imply that various pacing algorithms are useful as a nonpharmacologic method to prevent postoperative AF.     

Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: safety results from a phase I trial

Critical limb ischemia (CLI) is typified by rest pain and/or tissue necrosis secondary to advanced peripheral arterial disease (PAD) and is characterized by diminution in limb perfusion at rest. We tested the safety of an angiogenic strategy with CI-1023 (Ad(GV)VEGF121.10), a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121 in patients with CLI as part of a phase I trial. Fifteen subjects >35 years of age with CLI and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x 10(8) to 4 x 10(10) particle units, n = 13) or placebo (n = 2). All of the patients tolerated the injection well and there were no serious complications related to the procedure. Transient edema was noted in one patient. A total of 79 adverse events were reported over the course of one year. One death (day 136) and one malignancy (day 332) occurred in the CI-1023 group. CI-1023 appears to be well tolerated and safe for single-dose administration in patients with critical limb ischemia due to PAD. Further studies are needed to determine the efficacy of this form of therapeutic angiogenesis.