Interval to biochemical failure as a biomarker for cause-specific and overall survival after dose-escalated external beam radiation therapy for prostate cancer

BACKGROUND:

After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT.

METHODS:

From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated.

RESULTS:

There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS (P < .0001) but not OS (P = .36). However, a short interval to biochemical failure predicted decreased CSS (P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS (P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure (P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality (P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not.

CONCLUSIONS:

The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society.     

Purified c‐phycoerythrin: safety studies in rats and protective role against permanganate‐mediated fibroblast‐DNA damage

We have evaluated in vitro cytotoxicity of cyanobacterial phycoerythrin (C‐PE) on three human cell lines by cell proliferation and neutral red uptake assays. No toxic effects of C‐PE were observed to any of the cell lines tested. The protective role of purified C‐PE to potassium permanganate‐mediated human fibroblast‐DNA damage was assessed by comet assay at 0 (control), 10 and 20 µg C‐PE ml^?1 doses in pre‐, simultaneous and post‐mutagen exposure conditions. Significant DNA damage was detected only in post‐mutagen exposure conditions. Our findings confirmed that the C‐PE is non‐toxic and provides protection against permanganate‐mediated DNA damage. The preliminary acute (2000 mg C‐PE kg^?1 body weight, b.w.) and 90 day sub‐chronic (0, 5, 15 and 25 mg C‐PE kg^?1 b.w./day) oral toxicity studies of purified C‐PE in male albino rats showed no mortality or treatment‐related major clinical signs, and all the doses of C‐PE were well tolerated. The no observed adverse effect level and no observed effect level were found to be 15 and 5 mg C‐PE kg^?1 b.w./day respectively. Copyright © 2010 John Wiley & Sons, Ltd.     

Esomeprazole induced galactorrhea: a novel side effect

Proton pump inhibitors (PPIs) are one of the most frequently prescribed medications across the globe. Esomeprazole is the S-isomer of omeprazole, and it is currently the most widely prescribed PPI. The safety profile of esomeprazole is extremely favorable with only minor side effects, like headache and diarrhea, that are encountered in day to day practice. We report a case of a young female with symptoms of gastroesophageal reflux disease who developed galactorrhea after starting esomeprazole therapy. Resolution of galactorrhea after stopping the drug and self-rechallenge by the patient herself with reappearance of galactorrhea confirmed the culprit to be esomeprazole only. We postulate that esomeprazole may have a mild inhibitory effect on CYP3A4, which leads to decreased metabolism of estrogen, thereby increasing serum estrogen levels. Estrogen causes stimulation and production of prolactin release, which results in development of galactorrhea. This is the first case of esomeprazole induced galactorrhea, to the best of our knowledge.     

Identification of Nonalcoholic Fatty Liver Disease following Pancreatic Surgery in a Western Cohort Using a Novel Radiographic Technique

Background and Aims: While traditional risk factors for the development of nonalcoholic fatty liver disease (NAFLD) relate to metabolic syndrome, several Asian studies have suggested a high rate of de novo NAFLD following pancreaticoduodenectomy (PD). The aim of this study is to identify de novo NAFLD after pancreatic surgery and its associated risk factors. Methods: A retrospective cohort of patients at a single center that underwent PD or distal pancreatectomy (DP) over 7 years was identified. Pre- and postoperative contrast-enhanced computed tomography scans of the abdomen were reviewed, including attenuation measurements of the liver, spleen, and muscle. Primary outcomes included hepatic attenuation, liver to muscle ratio (LMR), and liver to spleen ratio (LSR). Results: Of the 96 patients (mean age 64.3) included, 70% underwent PD, and 30% underwent DP. The mean LMR decreased significantly from 1.81 to 1.66 (p=0.02), noted only in men. No interaction effect with LMR was observed with surgical type, chemotherapy, blood loss, pancreatic enzyme replacement, or transaminases. LMR decreased in 55% of subjects. Conclusions: Increased fatty infiltration, as evidence by decreased LMR, was found among men that underwent PD and DP within a year of surgery. This may be related to weight loss and malabsorption and deserves further investigation.