The Effectiveness of Intraoperative Clip Placement in Improving Radiation Therapy Boost Targeting After Oncoplastic Surgery

PURPOSE: The role of surgical clips as markers of the tumor bed cavity for radiation therapy boost targeting after oncoplastic surgery is not well understood. Therefore, we sought to evaluate whether the placement of surgical clips can reduce interobserver variability in the delineation of the tumor bed cavities of oncoplastic surgery patients and ultimately determine an optimal number of clips to place. METHODS AND MATERIALS: We reviewed records of 39 women with breast cancer who underwent oncoplastic breast surgery and adjuvant radiation therapy at our institution. Three radiation oncologists contoured tumor bed cavity volumes on planning computed tomography simulation images. Interobserver variability was measured both by a coefficient of variation of radiation oncologists contour volume and a concordance index defined as the quotient of the intersecting and aggregated volume of the contours. Patients were stratified by the number of surgical clips placed and compared by 1-way analysis of variance. Simple linear regression was used to evaluate the relationship of total excised volume and interobserver variability in patients with a sufficient quantity of surgical clips. RESULTS: Interobserver variability in the delineation of the tumor bed cavity as measured by concordance index was significantly reduced in patients who received intraoperative surgical clips (F = 5.755; P = .001). A similar trend was seen in contour volume (F = 2.616; P = .052). Results of 1-way analysis of variance and post hoc analysis showed that 4 clips are effective and sufficient for reproducible delineation of the tumor bed cavity for the radiation therapy boost. Increasing excision volume does not result in an increase in interobserver variability (r(2) = 0.00003). CONCLUSIONS: In oncoplastic surgery patients, intraoperative placement of surgical clips is beneficial and effective in improving the delineation of the tumor bed cavity for the radiation therapy boost. Four clips are necessary and sufficient for accurate boost targeting after lumpectomy with oncoplastic reconstruction

Analytical performance of thrombospondin-1 and cathepsin D immunoassays part of a novel CE-IVD marked test as an aid in the diagnosis of prostate cancer.

The Prostate Specific Antigen (PSA) test suffers from low specificity for the diagnosis of Prostate Cancer (PCa). We originally discovered two cancer-related proteins thrombospondin-1 (THBS1) and cathepsin D (CTSD) using a mass-spectrometry-based proteomics approach. The two serum proteins were shown to improve the diagnosis of high-grade PCa. Thus, we developed quantitative ELISAs for the determination of their concentration in human serum. Here we report their analytical performance in terms of limit of detection, specificity, precision, linearity and interferences, which were determined based on CLSI guidelines. Further, we investigated the influence of pre-analytical factors on concentration measurements. For this, blood from 4-6 donors was collected in different tubes and stored at room temperature for different times prior to centrifugation at different centrifugal forces and temperatures. Stability of THBS1 and CTSD under different storage temperatures was also evaluated. Our results show that the assays are specific, linear and sensitive enough to allow measurement of clinical samples. Precision in terms of repeatability and total within-laboratory coefficient of variation (CV) are 5.5% and 8.1% for THBS1 and 4.3% and 7.2% for CTSD, respectively. Relative laboratory-to-laboratory differences were -6.3% for THBS1 and -3% for CTSD. Both THBS1 and CTSD were stable in serum samples, with 80-120% recoveries of concentrations across donors, sample preparation and storage. In conclusion, the ELISAs as part of the novel commercial in vitro diagnostic test Proclarix are suitable for the use in clinical practice. THBS1 and CTSD can be accurately measured for their intended use independent of the lot and laboratory when conditions consistent with routine practice for PSA sampling and storage are used

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

Poly(ADP-ribose) polymerases (PARPs) are NAD(+) dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD(+)-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD(+) substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD(+) homeostasis