Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy

PURPOSE: Long-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment. METHODS: One hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS. RESULTS: The median length of follow-up was 8.3 years (range, 1.2–10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05). CONCLUSION: Disease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies

Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways

Geographic variation in plant community structure of salt marshes: species, functional and phylogenetic perspectives.

In general, community similarity is thought to decay with distance; however, this view may be complicated by the relative roles of different ecological processes at different geographical scales, and by the compositional perspective (e.g. species, functional group and phylogenetic lineage) used. Coastal salt marshes are widely distributed worldwide, but no studies have explicitly examined variation in salt marsh plant community composition across geographical scales, and from species, functional and phylogenetic perspectives. Based on studies in other ecosystems, we hypothesized that, in coastal salt marshes, community turnover would be more rapid at local versus larger geographical scales; and that community turnover patterns would diverge among compositional perspectives, with a greater distance decay at the species level than at the functional or phylogenetic levels. We tested these hypotheses in salt marshes of two regions: The southern Atlantic and Gulf Coasts of the United States. We examined the characteristics of plant community composition at each salt marsh site, how community similarity decayed with distance within individual salt marshes versus among sites in each region, and how community similarity differed among regions, using species, functional and phylogenetic perspectives. We found that results from the three compositional perspectives generally showed similar patterns: there was strong variation in community composition within individual salt marsh sites across elevation; in contrast, community similarity decayed with distance four to five orders of magnitude more slowly across sites within each region. Overall, community dissimilarity of salt marshes was lowest on the southern Atlantic Coast, intermediate on the Gulf Coast, and highest between the two regions. Our results indicated that local gradients are relatively more important than regional processes in structuring coastal salt marsh communities. Our results also suggested that in ecosystems with low species diversity, functional and phylogenetic approaches may not provide additional insight over a species-based approach

Case-Matched Outcomes of Proton Beam and Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Purpose: Although both intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) offer effective long-term disease control for localized prostate cancer (PCa), there are limited data directly comparing the 2 modalities. Methods: The data from 334 patients treated with conventionally fractionated (79.2 GyRBE in 44 fractions) PBT or IMRT were retrospectively analyzed. Propensity score matching was used to balance factors associated with biochemical failure-free survival (BFFS). Age, race, and comorbidities (not BFFS associates) remained imbalanced after matching. Univariable and covariate-adjusted multivariable (MVA) Cox regression models were used to determine if modality affected BFFS. Results: Of 334 patients, 176 (52.7%) were included in the matched cohort with exact matching to National Comprehensive Cancer Network (NCCN) risk group. With a median follow-up time of 9.0 years (interquartile range [IQR]: 7.8-10.2 years), long-term BFFS was similar between the IMRT and PBT matched arms with 8-year estimates of 85% (95% CI: 76%-91%) and 91% (95% CI: 82%-96%, P = .39), respectively. On MVA, modality was not significantly associated with BFFS in both the unmatched (hazard ratio [HR] = 0.75, 95% CI: 0.35-1.63, P = .47) and matched (HR = 0.87, 95% CI: 0.33-2.33, P = .78) cohorts. Prostate cancer-specific survival (PCSS) and overall survival (OS) were also similar (P &gt; .05). However, in an unmatched analysis, the PBT arm had significantly fewer incidences of secondary cancers within the irradiated field (0.6%, 95% CI: 0.0%-3.1% versus 4.5%, 95% CI: 1.8%-9.0%, P = .028). Conclusions: Both PBT and IMRT offer excellent long-term disease control for PCa, with no significant differences between the 2 modalities in BFFS, PCSS, and OS in matched patients. In the unmatched cohort, fewer incidences of secondary malignancy were noted in the PBT group; however, owing to overall low incidence of secondary cancer and imbalanced patient characteristics between the 2 groups, these data are strictly hypothesis generating and require further investigation.</p