[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to review all articles published in two temporarily available radiation oncology journals (Radiation Oncology Investigations, Journal of Radiosurgery) in order to evaluate their scientific impact. From several potential measures of impact and relevance of research, we selected article citation rate because landmark or practice-changing research is likely to be cited frequently. The citation database Scopus was used to analyse number of citations. During the time period 1996-1999 the journal Radiation Oncology Investigations published 205 articles, which achieved a median number of 6 citations (range 0-116). However, the most frequently cited article in the first 4 volumes achieved only 23 citations. The Journal of Radiosurgery published only 31 articles, all in the year 1999, which achieved a median number of 1 citation (range 0-11). No prospective randomized studies or phase I-II collaborative group trials were published in these journals. Apparently, the Journal of Radiosurgery acquired relatively few manuscripts that were interesting and important enough to impact clinical practice. Radiation Oncology Investigations' citation pattern was better and closer related to that reported in several previous studies focusing on the field of radiation oncology. The vast majority of articles published in temporarily available radiation oncology journals had limited clinical impact and achieved few citations. Highly influential research was unlikely to be submitted during the initial phase of establishing new radiation oncology journals.
[Show abstract][Hide abstract] ABSTRACT: Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases.
Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013).
The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100.
Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup.
Clinical and Translational Oncology 08/2015; DOI:10.1007/s12094-015-1340-9 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.
Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.
Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.
miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.
PLoS ONE 03/2015; 10(3):e0118745. DOI:10.1371/journal.pone.0118745 · 3.23 Impact Factor