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Abstract Background Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).

Abstract Background 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. Methods 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. Results 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 (p < 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. Conclusions 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.

JaHyun Kim Haboush, ed. Epistolary Korea: Letters in the Communicative Space of the Choson, 1392-1910. New York: Columbia UP, 2009. 336 pp. ISBN 978-0231148030, $27.50. JaHyun Kim Haboush's Epistolary Korea, [...]

The Imjin War: Japan's Sixteenth-Century Invasion of Korea and Attempt to Conquer China, by Samuel Hawley. Seoul: Royal Asiatic Society, Korea Branch, Publications and Berkeley: Institute of East Asian Studies, [...]

Background. Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate specific antigen (PSA) kinetics after prostate SBRT have not been well characterized. The purpose of this study was to analyze the trend in PSA decline following robotic SBRT from a prospective cohort of patients. Material and methods. In total 175 patients were treated definitively for localized prostate cancer to a dose of 35-36.25 Gy in 5 fractions using robotic SBRT in the absence of androgen deprivation therapy (ADT). PSA and testosterone were collected at regular intervals following treatment and patients were assessed for biochemical failure and benign PSA bounce. A PSA nadir threshold of 0.5 ng/ml was used as a predictor of long-term disease-free survival. Multivariate logistic regression was used to assess the effect of disease specific covariates on the likelihood of achieving a PSA nadir less than threshold. PSA kinetics were analyzed a multi-component exponential model accounting for benign and malignant sources of PSA. Results and conclusion. At a median follow-up of 3 years, 70% of patients achieved a PSA nadir below 0.5 ng/ml with a median PSA nadir of 0.3 ng/ml at a median time to nadir of 30 months. In our cohort, 36.2% experienced a benign PSA bounce. Absence of PSA bounce, initial PSA, and testosterone at the time of nadir proved to be significant predictors of achieving a PSA nadir below threshold. PSA kinetics after prostate SBRT were well described with a functional volume model with fitted half-lives of 4.4 and 14.8 months for malignant and benign sources of PSA, respectively. Patients treated with prostate SBRT experience an initial period of rapid PSA decline followed by a slow decline which will likely result in lower PSA nadirs after longer follow-up. The long-term disease specific impacts of these results remain to be determined. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. Consensus regarding the appropriate patient-reported outcome (PRO) endpoints for clinical trials evaluating radiation modalities for early stage prostate cancer is lacking. To aid in clinical trial design, this study presents PROs over a 36-month period following SBRT for clinically localized prostate cancer. Methods: Between February 2008 and September 2010, 174 hormone-naïve patients with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT (CyberKnife, Accuray) delivered in 5 fractions. Patients completed the validated Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire at baseline and all follow-ups. The proportion of patients developing a clinically significant decline in each EPIC domain score was determined. The minimally important difference (MID) was defined as a change of one-half the standard deviation from the baseline. Per Radiation Therapy Oncology Group (RTOG) 0938, we also examined the patients who experienced a decline in EPIC urinary domain summary score of >2 points (unacceptable toxicity defined as ⩾60% of all patients reporting this degree of decline) and EPIC bowel domain summary score of >5 points (unacceptable toxicity defined as >55% of all patients reporting this degree of decline) from baseline to 1 year. Results: A total of 174 patients at a median age of 69 years received SBRT with a minimum follow-up of 36 months. The proportion of patients reporting a clinically significant decline (MID for urinary/bowel are 5.5/4.4) in EPIC urinary/bowel domain scores was 34%/30% at 6 months, 40%/32.2% at 12 months, and 32.8%/21.5% at 36 months. The patients reporting a decrease in the EPIC urinary domain summary score of >2 points was 43.2% (CI: 33.7%, 54.6%) at 6 months, 51.6% (CI: 43.4%, 59.7%) at 12 months, and 41.8% (CI: 33.3%, 50.6%) at 36 months. The patients reporting a decrease in the EPIC bowel domain summary score of >5 points was 29.6% (CI: 21.9%, 39.3%) at 6 months, 29% (CI: 22%, 36.8%) at 12 months, and 22.4% (CI: 15.7%, 30.4%) at 36 months. Conclusion: Following prostate SBRT, clinically significant urinary symptoms are more common than bowel symptoms. Our prostate SBRT treatment protocol meets the RTOG 0938 criteria for moving forward to a Phase III trial comparing it to conventionally fractionated radiation therapy. Notably, between 12 and 36 months, the proportion of patients reporting a significant decrease in both EPIC urinary and bowel domain scores declined, suggesting a late improvement in these symptom domains. Further investigation is needed to elucidate (1) which EPIC domains bear the greatest influence on post-treatment quality of life and (2) at what time point PRO endpoint(s) should be assessed. [ABSTRACT FROM AUTHOR]

Background: Patients with large prostate volumes have been shown to have higher rates of genitourinary and gastrointestinal toxicities after conventional radiation therapy for prostate cancer. The efficacy and toxicity of stereotactic body radiation therapy (SBRT), which delivers fewer high-dose fractions of radiation treatment, is unknown for large prostate volume prostate cancer patients. We report our early experience using SBRT for localized prostate cancer in patients with large prostate volumes. Methods: 57 patients with prostate volumes ≥50 CM3 prior to treatment with SBRT for localized prostate carcinoma and with a minimum follow up of two years were included in this retrospective review of prospectively collected data. Treatment was delivered using Cyberknife (Accuray) with doses of 35–36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were scored using the CTCAE v.4. Quality of life was assessed using the American Urological Association (AUA) Symptom Score and the Expanded Prostate Cancer Index Composite (EPIC)-26. Results: 57 patients (23 low-, 25 intermediate- and 9 high-risk according to the D’Amico classification) at a median age of 69 years (range, 54–83 years) received SBRT with a median follow-up of 2.9 years. The median prostate size was 62.9 CM3 (range 50–138.7 CM3). 33.3% of patients received ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.5 ng/ml and decreased to a median PSA of 0.4 ng/ml by 2 years (p <0.0001). A mean baseline AUA symptom score of 7.5 significantly increased to 13 at 1 month (p = 0.001) and returned to baseline by 3 months (p = 0.21). 23% of patients experienced a late transient urinary symptom flare in the first two years following treatment. Mean baseline EPIC bowel scores of 95.8 decreased to 78.1 at 1 month (p <0.0001), but subsequently improved to 93.5 three months (p = 0.08). The 2-year actuarial incidence rates of GU and GI toxicity ≥ grade 2 were 49.1% and 1.8%, respectively. Two patients (3.5%) experienced grade 3 urinary toxicity, and no patient experienced grade 3 gastrointestinal toxicity. Conclusions: SBRT for clinically localized prostate cancer was well tolerated in men with large prostate volumes. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common side-effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment. Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months follow-up were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post- SBRT. Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (p=0.02). Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC) quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA) levels, testosterone levels, tumor stage, and treatment variables were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side-effect of SBRT. In contrast to standard radiation therapy, results suggest SBRT-related fatigue is short-term rather than a longterm side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 posttreatment 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. Results: 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 (p < 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. [ABSTRACT FROM AUTHOR]

Background: Patients with large prostate volumes have been shown to have higher rates of genitourinary and gastrointestinal toxicities after conventional radiation therapy for prostate cancer. The efficacy and toxicity of stereotactic body radiation therapy (SBRT), which delivers fewer high-dose fractions of radiation treatment, is unknown for large prostate volume prostate cancer patients. We report our early experience using SBRT for localized prostate cancer in patients with large prostate volumes. Methods: 57 patients with prostate volumes ≥50 CM3 prior to treatment with SBRT for localized prostate carcinoma and with a minimum follow up of two years were included in this retrospective review of prospectively collected data. Treatment was delivered using Cyberknife (Accuray) with doses of 35–36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were scored using the CTCAE v.4. Quality of life was assessed using the American Urological Association (AUA) Symptom Score and the Expanded Prostate Cancer Index Composite (EPIC)-26. Results: 57 patients (23 low-, 25 intermediate- and 9 high-risk according to the D’Amico classification) at a median age of 69 years (range, 54–83 years) received SBRT with a median follow-up of 2.9 years. The median prostate size was 62.9 CM3 (range 50–138.7 CM3). 33.3% of patients received ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.5 ng/ml and decreased to a median PSA of 0.4 ng/ml by 2 years (p <0.0001). A mean baseline AUA symptom score of 7.5 significantly increased to 13 at 1 month (p = 0.001) and returned to baseline by 3 months (p = 0.21). 23% of patients experienced a late transient urinary symptom flare in the first two years following treatment. Mean baseline EPIC bowel scores of 95.8 decreased to 78.1 at 1 month (p <0.0001), but subsequently improved to 93.5 three months (p = 0.08). The 2-year actuarial incidence rates of GU and GI toxicity ≥ grade 2 were 49.1% and 1.8%, respectively. Two patients (3.5%) experienced grade 3 urinary toxicity, and no patient experienced grade 3 gastrointestinal toxicity. Conclusions: SBRT for clinically localized prostate cancer was well tolerated in men with large prostate volumes. [ABSTRACT FROM AUTHOR]