Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

<p>Abstract</p> <p>Background</p> <p>The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.</p> <p>Methods</p> <p>Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.</p> <p>Results</p> <p>All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (<it>p </it>< 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.</p> <p>Conclusions</p> <p>Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.</p

Effect of Tillage and Planting Date on Seasonal Abundance and Diversity of Predacious Ground Beetles in Cotton

A 2-year field study was conducted in the southern High Plains region of Texas to evaluate the effect of tillage system and cotton planting date window on seasonal abundance and activity patterns of predacious ground beetles. The experiment was deployed in a split-plot randomized block design with tillage as the main-plot factor and planting date as the subplot factor. There were two levels for each factor. The two tillage systems were conservation tillage (30% or more of the soil surface is covered with crop residue) and conventional tillage. The two cotton planting date window treatments were early May (normal planting) and early June (late planting). Five prevailing predacious ground beetles, Cicindela sexguttata F., Calosoma scrutator Drees, Pasimachus spp., Pterostichus spp., and Megacephala Carolina L. (Coleoptera: Carabidae), were monitored using pitfall traps at 2-week intervals from June 2002 to October 2003. The highest total number of ground beetles (6/trap) was observed on 9 July 2003. Cicindela sexguttata was the dominant ground dwelling predacious beetle among the five species. A significant difference between the two tillage systems was observed in the abundances of Pterostichus spp. and C. sexguttata. In 2002. significantly more Pterostichus spp. were recorded from conventional plots (0.27/trap) than were recorded from conservation tillage plots (0.05/trap). Significantly more C. sexguttata were recorded in 2003 from conservation plots (3.77/trap) than were recorded from conventional tillage plots (1.04/trap). There was a significant interaction between year and tillage treatments. However, there was no significant difference in the abundances of M. Carolina and Pasimachus spp. between the two tillage practices in either of the two years. M. Carolina numbers were significantly higher in late-planted cotton compared with those observed in normal-planted cotton. However, planting date window had no significant influence on the activity patterns of the other species. Ground beetle species abundance, diversity, and species richness were significantly higher in conservation tillage plots. This suggests that field conditions arising from the practice of conservation tillage may support higher predacious ground beetle activity than might be observed under field conditions arising from conventional tillage practices

Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens

Historically, it has been difficult to propagate cells in vitro that are derived directly from human tumors or healthy tissue. However, in vitro preclinical models are essential tools for both the study of basic cancer biology and the promotion of translational research, including drug discovery and drug target identification. This protocol describes conditional reprogramming (CR), which involves coculture of irradiated mouse fibroblast feeder cells with normal and tumor human epithelial cells in the presence of a Rho kinase inhibitor (Y-27632). CR cells can be used for various applications, including regenerative medicine, drug sensitivity testing, gene expression profiling and xenograft studies. The method requires a pathologist to differentiate healthy tissue from tumor tissue, and basic tissue culture skills. The protocol can be used with cells derived from both fresh and cryopreserved tissue samples. As approximately 1 million cells can be generated in 7 d, the technique is directly applicable to diagnostic and predictive medicine. Moreover, the epithelial cells can be propagated indefinitely in vitro, yet retain the capacity to become fully differentiated when placed into conditions that mimic their natural environment

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy

Proctitis following stereotactic body radiation therapy for prostate cancer

Background Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. Methods Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. Results The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. Conclusions In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations

Urinary Estrogen Metabolites and Prostate Cancer Risk: A Pilot Study

BACKGROUND: The high incidence of and few identified risk factors for prostate cancer underscore the need to further evaluate markers of prostate carcinogenesis. The aim of this pilot study was to evaluate urinary estrogen metabolites as a biomarker of prostate cancer risk. METHODS: Using a liquid chromatography-tandem mass spectrometry method, urinary concentrations of 15 estrogen metabolites were determined in 77 prostate cancer cases, 77 healthy controls, and 37 subjects who had no evidence of prostate cancer after a prostate biopsy. RESULTS: We observed an inverse association between the urinary 16-ketoestradiol (16-KE2) and 17-epiestriol (17-epiE3)--metabolites with high estrogenic activity--and prostate cancer risk. Men in the lowest quartile of 16-KE2, had a 4.6-fold risk of prostate cancer (OR=4.62, 95% CI=1.34-15.99), compared with those in the highest quartile. CONCLUSIONS: We observed modest differences in estrogen metabolite concentrations between prostate cancer patients and subjects without cancer. Larger studies with both androgen and estrogen measurements are needed to confirm these results to clarify further whether estrogen metabolites are independent biomarkers for prostate cancer risk and whether androgen/estrogen imbalance influences prostate cancer risk