Upfront Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy in Elderly Patients with Brain Metastases from Non-small cell lung cancer: A Retrospective Analysis of a 10-Year Bi-Institutional Experience.

Purpose: Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) are increasingly used as initial therapies for brain metastases (BM). We aimed to assess the outcomes of SRS/FSRT in patients aged ≥65 years who had 1-10 BM from non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively reviewed 91 elderly NSCLC patients with 222 BM who were treated with SRS/FSRT at two institutions between 2010 and 2020. The primary endpoint was overall survival (OS) after SRS/FSRT. In addition, in-field local control (IFLC) within the treated field was evaluated. Statistical analysis was performed to identify the prognostic factors affecting OS and IFLC. Results: During a median follow-up of 18 months, the median OS was 32 months. The 1- and 2-year survival rates were 69.8 and 56.1%, respectively. In multivariate analysis, the NSCLC-specific graded prognostic assessment (GPA) score (p=0.007) and administration of systemic therapy (p=0.039) were defined as prognosticators affecting OS. The median IFLC period was 31 months, and the 1- and 2-year IFLC rates were 75.9 and 57.6%, respectively. The total BM volume (p=0.042) significantly affected IFLC. No severe adverse events were reported after SRS/FSRT. Conclusion: SRS/FSRT is an effective upfront treatment option for BM arising from NSCLC in elderly patients, with a good OS without severe side effects. Higher GPA score and active systemic treatment were associated with improved OS, indicating that elderly patients are significant candidates for SRS/FSRT.

Definitive radiotherapy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: A multicenter retrospective study (KROG 21-10).

PURPOSE: To assess the failure pattern and analyze the treatment scheme of definitive radiation therapy (RT) for T1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We performed a multi-institutional retrospective analysis in T1N0M0 ESCC patients who underwent definitive RT from 2010 to 2019. Patterns of failure were demonstrated as in-, and out-field locoregional, and distant metastasis. In the analysis, freedom-from locoregional recurrence (FFLRR) and their association with clinicopathologic factors were evaluated. Propensity score matching in cT1b patients was done. RESULTS: 168 patients were included with a median follow-up of 34.0 months, and 26 cT1a, 116 cT1b disease. The rates of 3-year all and locoregional recurrence for cT1a were 30.5% and 24.1% and those for cT1b were 27.1% and 25.9%, respectively. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5%. There was no difference between ENI and IFI in FFLRR (P = 0.831) and OS (P = 0.525). The 3-year FFLRR was 83.8% (95% Confidence interval (CI), 61.8-93.8%) in IFI group and 85.3% (95% CI, 65.1-94.3%) in ENI group. In multivariate analysis, concurrent chemotherapy use was marginally associated with FFLRR (Hazard ratio, 0.16; P = 0.064). CONCLUSION: cT1a patients who cannot receive endoscopic resection showed similar failure rates as cT1b patients, questioning the staging accuracy and raised the need for thorough treatment like chemoradiotherapy. In cT1b patients, IFI with 50 to 60 Gy and concurrent chemotherapy could be reasonable.

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation.

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

PURPOSE: We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. RESULTS: During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CONCLUSION: CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

Tumor volume and sphericity as predictors of local control after stereotactic radiosurgery for limited number (1-4) brain metastases from nonsmall cell lung cancer.

AIM: This study aims to evaluate the usage of brain metastases (BM) tumor volume and sphericity as prognostic factors in local control (LC) after stereotactic radiosurgery (SRS) for limited number (1-4) BM from nonsmall cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 80 patients, with 141 BM, who were treated with SRS from 2012 to 2017. Local failure was defined as an increase in lesion size after SRS. LC and overall survival (OS) were estimated using Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. RESULTS: The median clinical and radiographic follow-up was 11.2 and 9.0 months, respectively. The median BM tumor volume was 0.31 cm3 (0.01-21.64 cm3 ) and the median tumor sphericity was 0.76 (0.39-0.95). The median LC of the entire cohort was 28.8 months. LC rate at last follow-up was achieved in 84.4% of patients (35.5% CR, 35.5% PR, and 13.5% SD). LC was 83.8% at 1 year and 56.3% at 2 years. On multivariate analysis, only sphericity (P < .001) and volume (P = .004) were found to be a strong predictor for LC. The median OS of the entire cohort was 24.1 months. On multivariate analysis, only GPA score was found to be a predictor for OS. CONCLUSION: BM tumor sphericity and volume were found to be strong predictors for LC. Tumor sphericity and volume should be taken into consideration when treating patients with BM and when designing future prospective studies and developing prognostic indices.

Protein Hydrolysate of Silkworm Pupa Prevents Memory Impairment Induced by Oxidative Stress in Scopolamine-Induced Mice via Modulating the Cholinergic Nervous System and Antioxidant Defense System.

Silkworm pupae (Bombyx mori) is an edible insect that has been reported to contain high-quality proteins, lipids, minerals, and vitamins, and to possess high antioxidant activity. However, there have been no studies on the neuroprotective effects of silkworm pupae. Therefore, we investigated a water extract of silkworm pupae with protease (WSP) as a functional and therapeutic candidate for neurodegenerative disorders. First, we evaluated the effect of WSP on oxidative stress-induced mouse hippocampal neuronal cells (HT-22 cells). Cell viability diminished by addition of glutamate but was significantly recovered by WSP treatment. Furthermore, WSP significantly decreased the release of lactate dehydrogenase and generation of intracellular reactive oxygen species in oxidative stress-induced cells. In addition, in scopolamine-treated mice, WSP attenuated memory impairment, as demonstrated in the Morris water maze and passive avoidance tests, indicating protection of neuronal cells against oxidative damage. Moreover, WSP prevented scopolamine-induced increases in acetylcholinesterase activity and decreases in choline-acetyltransferase activity. Finally, treatment with WSP enhanced the antioxidant defense system by regulating the activities of antioxidant enzymes. Overall, this study showed that WSP exerted antioxidant and memory enhancing action against oxidative stress.

Efficacy of Polygonatum sibiricum on Mild Insomnia: A Randomized Placebo-Controlled Trial.

Polygonatum sibiricum (PS) rhizome, which contains glyceryl-1-monolinoleate as its primary active component, has been shown to improve insomnia in animal models. Based on these findings, we aimed to investigate the safety and efficacy of PS rhizome extract in improving sleep quality in individuals with mild insomnia. Eighty individuals with mild insomnia were enrolled in a four-week, randomized, double-blind, placebo-controlled trial of PS rhizome extract (500 mg/day, n = 40, PS group) or placebo (n = 40, placebo group). The primary outcome measure was change in total score on the Athens Insomnia Scale (AIS) to indicate sleep quality. The secondary outcome measures included change in actigraphy data and perfusion levels in the brain regions within the default mode network (DMN), which is known to play a key role in insomnia. The PS group showed greater improvement in the total AIS score with a significant increase in total sleep time, relative to the placebo group. In addition, significant group-by-visit interactions were observed in the perfusion level of the medial prefrontal cortex within the DMN. Findings of the current study provide first evidence that PS rhizome extract could be an effective natural ingredient for improving sleep in mild insomnia using a human model.

Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp.

Collagen hydrolysate is a well-known nutritional supplement for the improvement of healthy skin. Here, collagen peptide NS (CPNS) from fish scale was prepared, and its physicochemical properties were investigated. Gly-Pro was revealed as a representative low molecular weight peptide of CPNS, by performing prep-HPLC and LC-MS/MS. CPNS treatment attenuated matrix metalloproteinase-1 production and increased the synthesis of type 1 procollagen in HDF cells. After orally administering CPNS to rats, the plasma concentrations of Gly-Pro and Pro-Hyp increased dramatically. To examine the protective effects of CPNS against ultraviolet B (UVB)-induced photoaging in vivo, the dorsal skins of hairless mice were exposed to UVB and supplemented with CPNS for 12 weeks. The CPNS consumption significantly attenuated UVB-induced wrinkle formation, transepidermal water loss, and epidermis thickness, and increased skin hydration. Collectively, these results suggest that bioactive peptides of CPNS, Gly-Pro and Pro-Hyp, exert beneficial effects on skin health.

Long-term results and PSA kinetics after robotic SBRT for prostate cancer: multicenter retrospective study in Korea (Korean radiation oncology group study 15-01).

BACKGROUND: To evaluate the treatment outcome and prostate-specific antigen (PSA) change after stereotactic body radiotherapy (SBRT) for localized prostate cancer. METHODS: Patients with localized prostate cancer treated with SBRT at three academic hospitals were enrolled. Treatment was delivered using Cyberknife with dose range from 35 to 37.5 Gy in 5 fractions. Biochemical failure (BCF) was assessed with Phoenix definition and toxicities were scored with Radiation Therapy Oncology Group (RTOG) toxicity criteria. The PSA kinetics were analyzed in patients who received no androgen deprivation therapy (ADT) and showed no recurrence. RESULTS: Of the total 88 patients, 14 patients (15.9%) received ADT. After median follow-up of 63.8 months, the 5-year BCF free survival (BCFFS) was 94.7%. Two patients experienced late grade ≥ 3 GI toxicities (2.2%). The median nadir PSA was 0.12 ng/mL (range, 0.00-2.62 ng/mL) and the median time to nadir was 44.8 months (range, 0.40-85.7 months). Patients who reached nadir before 24 months showed poorer BCFFS than the others. The rate of PSA decline was maximum in the first year after treatment and gradually decreased with time. The pattern of PSA change was significantly different according to the risk groups (p = 0.011) with the slope of - 0.139, - 0.161 and - 0.253 ng/mL/month in low-, intermediate- and high-risk groups, respectively. CONCLUSION: SBRT for localized prostate cancer showed favorable efficacy with minimal toxicities. The time to PSA nadir was significantly associated with treatment outcome. PSA revealed rapid initial decline and slower decrease with longer follow-up and the patterns of PSA changes were different according to the risk groups.

Metabolic positron emission tomography parameters predict failure patterns in early non-small-cell lung cancer treated with stereotactic body radiation therapy: a single institution experience.

OBJECTIVE: The prognostic value of metabolic parameters using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has not been established for early non-small cell lung cancer (NSCLC). Accordingly, the authors investigated the prognostic value of metabolic parameters in terms of failure patterns in patients with early NSCLC who underwent stereotactic body radiation therapy (SBRT). METHODS: Data from 35 patients with Stage I NSCLC who underwent SBRT using CyberKnife and received pretreatment FDG PET/CT between 2008 and 2016 were retrospectively reviewed. Maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were measured. The significance of these parameters with regard to failure patterns was assessed. RESULTS: The median follow-up was 23 months for all patients and 34 months for living patients. Ten patients experienced recurrence: three local failures, five regional failures (RF), and eight distant failures (DF). Three-year local, regional and distant control rates were 96.7%, 86.4% and 71.1%, respectively. High SUVmax (<9 vs. ≥9) was an independent predictive factor associated with increased RF (P = 0.027) and DF (P = 0.008). Furthermore, SUVmax was indicative of both progression-free (P = 0.015) and overall (P = 0.034) survival. CONCLUSIONS: High SUVmax was a significant metabolic parameter associated with increased RF and DF in patients with early NSCLC who received SBRT, having a high propensity for dissemination. These results suggest that adjuvant treatment in conjunction with SBRT may be considered in patients with early NSCLC and high SUVmax.

In Vitro Evidence of Anti-Inflammatory and Anti-Obesity Effects of Medium-Chain Fatty Acid-Diacylglycerols.

Dietary approaches using structured lipids, including medium-chain fatty acids and diacylglycerols, have been adopted for the prevention of obesity-induced chronic inflammation. In an extension to previous studies, medium-chain fatty acid-diacylglycerol enriched dietary oil (MCDG) was prepared by interesterification of canola oil and mediumchain fatty acid-triacylglycerols. The consequent MCDG product was applied to RAW264.7 macrophages followed by the assessment of multiple inflammatory responses. Compared with conventionally used canola and olive oil controls, MCDG suppressed macrophage phagocytosis, as assessed by the uptake of microsphere beads. Furthermore, the production of IL-6 and TNF-α, transcription of COX-2 and iNOS, and expression of CD80 on cell surfaces were downregulated by MCDG in LPS-stimulated macrophages. Subsequently, differentiated 3T3-L1 adipocytes were evaluated for proinflammatory cytokine production and lipid accumulation. IL-6 production was marginally affected and lipid accumulation was inhibited by MCDG. Taken together, these results suggest that MCDG has potential as an alternative oil for cooking in order to prevent obesity-induced inflammation.

Medium-Chain Enriched Diacylglycerol (MCE-DAG) Oil Decreases Body Fat Mass in Mice by Increasing Lipolysis and Thermogenesis in Adipose Tissue.

Medium chain fatty acid (MCFA) escapes the formation of chylomicrons in the small intestine, resulting in energy expenditure through beta-oxidation. Diacylglycerol (DAG) is susceptible to oxidation rather than being stored in the adipose tissue. This study was conducted to verify the effect of MCE-DAG oil on body fat mass in vivo. Male C57BL/6 mice were randomly assigned to four groups (n = 12) as follows: (1) normal diet (18% kcal from fat), (2) canola oil as a control (40% kcal from canola oil), (3) MCE-DAG10 (10% kcal from MCE-DAG + 30% kcal from canola oil), and (4) MCE-DAG20 (20% kcal from MCE-DAG + 20% kcal from canola oil). The body weight and fat mass of MCE-DAG20 group mice were decreased relative to those of control mice (P < 0.05 and P < 0.001, respectively). Serum triacylglycerol (TAG) was decreased in both MCE-DAG10 and MCE-DAG20 groups (P < 0.01 and P < 0.05, respectively). Hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) were increased in the MCE-DAG20 group relative to the control in white adipose tissue (WAT) (P < 0.05). Uncoupling protein 1 (UCP1) was also increased in the MCE-DAG20 group relative to the control in brown adipose tissue (BAT) (P < 0.05). In summary, MCE-DAG reduced body fat mass likely by stimulating lipolysis in WAT and thermogenesis in BAT.

Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer.

AIM: We report our experience with Cyberknife to deliver hypofractionated stereotactic body radiotherapy (SBRT) boost combined with whole pelvis radiotherapy (WPRT) to patients with intermediate- to high-risk prostate cancer. METHODS: From March 2008 to July 2014, 39 patients with newly diagnosed, intermediate- and high-risk (National Comprehensive Cancer Network definition) localized prostate cancer were treated with WPRT and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy before biochemical relapse. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. RESULTS: Thirty-nine patients with a median 53.6 months (range 14-74 months) follow-up were analyzed. The median pretreatment PSA was 15.97 ng/mL. The estimated 5-year biochemical failure (BCF)-free survival was 94.7%. Two BCFs were observed in only high-risk group. The median PSA nadir was 0.30 ng/mL at median 36 months and PSA bounce occurred in 15.4% (n = 6) of patients at median 12 months. No grade 3 acute toxicity was noted. A total of 23% of the patients had grade 2 acute genitourinary (GU) toxicities and 21% had grade 2 acute gastrointestinal (GI) toxicities. At 2 months, most complications had returned to baseline. GU and GI toxicities were observed. CONCLUSIONS: WPRT followed by SBRT boost using Cyberknife in intermediate- and high-risk prostate cancer is feasible with minimal toxicity and encouraging BCF-free survival.

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost and whole pelvic radiotherapy for intermediate- and high-risk prostate cancer.

AIM: Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate specific antigen (PSA) kinetics after SBRT has not been well characterized. The objective of the current study is to analyze the rate of PSA decline and PSA nadir following SBRT boost after whole pelvis radiotherapy (WPRT) in intermediate- and high-risk prostate cancer. METHODS: From March 2008 to July 2014, 42 patients newly diagnosed, intermediate- and high-risk (NCCN definition) localized prostate cancer were treated with SBRT boost using Cyberknife after WPRT. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy (ADT) before biochemical relapse. PSA nadir and rate of change in PSA (slope) were calculated and compared. RESULTS: With a median follow-up of 53.6 months (range, 14-74), the median rates of decline of PSA were -0.605, -0.229 and -0.166 ng/mL/month, respectively, for durations of 1, 2 and 3 years postradiotherapy, respectively. The median PSA nadir was 0.32 ng/mL after a median 36 months. 4-year biochemical failure (BCF) free survival was 100 percent for intermediate-risk and 71.4 percent for high-risk patients (P = 0.002). CONCLUSIONS: In this report of intermediate- and high-risk prostate cancer, continuously greater rates of decline PSA for duration 1, 2 and 3 year following SBRT boost after WPRT resulted in lower PSA nadir. Also, SBRT boost after WBPT leads to favorable BCF-free survival.

The Predictive Value of Tumor Size, Volume, and Markers During Radiation Therapy in Patients With Cervical Cancer.

OBJECTIVES: We investigated the prognostic significance of changes in primary tumor volume and serum squamous cell carcinoma antigen (SCC-ag) levels during radiation therapy (RT) in patients with cervical cancer. METHODS: We conducted a review of 40 patients treated with RT. All patients received external beam RT and intracavitary brachytherapy. The primary tumor volume and squamous cell carcinoma antigen levels were measured pre-RT and mid-RT. Overall survival (OS) and progression free survival (PFS) were estimated, and possible prognostic factors for survival were analyzed. RESULTS: The correlation coefficient between primary tumor volume reduction rate (pTVRR) and serum squamous cell carcinoma antigen reduction rate in all patients was 0.550 (P < 0.001). In univariate analysis, stage more than II (P <0.001), pre-RT pTV of 55 cm or more (P = 0.05), mid-RT tumor size of 4 cm or more (P = 0.004), and pTVRR of 90% or less (P = 0.031) were significant unfavorable prognostic factors for PFS, whereas stage (P = 0.009) was the only significant prognostic factor for OS. Multivariable analysis revealed that none of these factors were independently associated with PFS or OS. CONCLUSIONS: There was a significant correlation between pTVRR and squamous cell carcinoma antigen reduction rate. Our findings indicate that the tumor parameters such as pre-RT pTV, mid-RT tumor size, and pTVRR are associated with PFS in women with cervical cancer.

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy versus conventionally fractionated external beam radiotherapy for low- and intermediate-risk prostate cancer.

AIM: The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between stereotactic body radiotherapy (SBRT) using Cyberknife and conventionally fractionated external beam radiotherapy (CF-EBRT) in low- and intermediate-risk prostate cancer. METHODS: A total of 69 patients with low- and intermediate-risk prostate cancer were enrolled. Thirty-four patients were treated with SBRT (36.25 Gy in five fractions) using Cyberknife and 35 patients treated with CF-EBRT (70.2-75.6 Gy in 39-42 fractions). PSA nadir, rate of PSA decline and biochemical failure (BCF) free survival were calculated and compared. RESULTS: With a median follow-up of 53.6 months (range, 14-74), the median slopes for SBRT were -0.430, -0.199, -0.127 and -0.094 ng/mL/month, respectively, for durations of 1, 2, 3 and 4 years following radiotherapy. Similarly, for CF-EBRT, the median slopes were -0.529, -0.138, -0.109 and -0.056 ng/mL/month, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year than SBRT (P = 0.018). Conversely, the slopes of SBRT for duration for 2, 3 and 4 year tended to be continuously greater than CF-EBRT (P = 0.028, P = 0.058 and P = 0.128, respectively). The significantly lower PSA nadir was observed in SBRT (nadir 0.23 ng/mL) compared with CF-EBRT (nadir 0.37 ng/mL) (P = 0.011). Five-year BCF free survivals were 100% for SBRT and 80.8% for CF-EBRT (P = 0.031). CONCLUSIONS: Patients treated with SBRT experienced a lower PSA nadir and tended to a continuously greater rate of decline of PSA for duration 2, 3 and 4 years than CF-EBRT. The improved PSA kinetics of SBRT leaded to favorable BCF-free survival.

Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma.

PURPOSE: Stereotactic body radiotherapy (SBRT) takes advantage of low α/ß ratio of prostate cancer to deliver a large dose in few fractions. We examined clinical outcomes of SBRT using CyberKnife for the treatment of low- and intermediate-risk prostate cancer. MATERIALS AND METHODS: This study was based on a retrospective analysis of the 33 patients treated with SBRT using CyberKnife for localized prostate cancer (27.3% in low-risk and 72.7% in intermediate-risk). Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. RESULTS: Thirty-three patients with a median 51 months (range, 6 to 71 months) follow-up were analyzed. There was no biochemical failure. Median PSA nadir was 0.27 ng/mL at median 33 months and PSA bounce occurred in 30.3% (n = 10) of patients at median at median 10.5 months after SBRT. No grade 3 acute toxicity was noted. The 18.2% of the patients had acute grade 2 genitourinary (GU) toxicities and 21.2% had acute grade 2 gastrointestinal (GI) toxicities. After follow-up of 2 months, most complications had returned to baseline. There was no grade 3 late GU and GI toxicity. CONCLUSION: Our experience with SBRT using CyberKnife in low- and intermediate-risk prostate cancer demonstrates favorable efficacy and toxicity. Further studies with more patients and longer follow-up duration are required.

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer. METHODS: A total of 77 patients with localized prostate cancer [T-stage, T1-T3; Gleason score (GS) 5-9; PSA < 20 ng/mL] were enrolled. A total of 35 patients were treated with SBRT boost (21 Gy in 3 fractions) after WP-EBRT and 42 patients were treated with CF-EBRT (45 Gy WP-EBRT and boost of 25.2-30.6 Gy in 1.8-Gy fractions). PSA nadir and rate of change in PSA (slope) were calculated and compared. RESULTS: With a median follow-up of 52.4 months (range, 14-74 months), the median PSA nadir and slope for SBRT boost were 0.29 ng/mL and -0.506, -0.235, -0.129, and -0.092 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for CF-EBRT, the median PSA nadir and slopes were 0.39 ng/mL and -0.720 ng/mL/mo, -0.204 ng/mL/mo, -0.121 ng/mL/mo, and -0.067 ng/mL/mo, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year postradiotherapy than that of SBRT boost (P = 0.018). Contrastively, the slopes of SBRT boost for durations of 2 years, 3 years, and 4 years tended to be continuously greater than that of CF-EBRT. The significantly lower PSA nadir was observed in SBRT boost (median nadir 0.29 ng/mL) compared with CF-EBRT (median nadir 0.35 ng/mL, P = 0.025). Five-year biochemical failure (BCF) free survival was 94.3% for SBRT boost and 78.6% for CF-EBRT (P = 0.012). CONCLUSION: Patients treated with SBRT boost after WP-EBRT experienced a lower PSA nadir and there tended to be a continuously greater rate of decline of PSA for durations of 2 years, 3 years, and 4 years than with CF-EBRT. The improved PSA kinetics of SBRT boost over CF-EBRT led to favorable BCF free survival.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma.

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.

Adipose Mesenchymal Stem Cell Secretome Modulated in Hypoxia for Remodeling of Radiation-Induced Salivary Gland Damage.

BACKGROUND AND PURPOSE: This study was conducted to determine whether a secretome from mesenchymal stem cells (MSC) modulated by hypoxic conditions to contain therapeutic factors contributes to salivary gland (SG) tissue remodeling and has the potential to improve irradiation (IR)-induced salivary hypofunction in a mouse model. MATERIALS AND METHODS: Human adipose mesenchymal stem cells (hAdMSC) were isolated, expanded, and exposed to hypoxic conditions (O2 < 5%). The hypoxia-conditioned medium was then filtered to a high molecular weight fraction and prepared as a hAdMSC secretome. The hAdMSC secretome was subsequently infused into the tail vein of C3H mice immediately after local IR once a day for seven consecutive days. The control group received equal volume (500 µL) of vehicle (PBS) only. SG function and structural tissue remodeling by the hAdMSC secretome were investigated. Human parotid epithelial cells (HPEC) were obtained, expanded in vitro, and then irradiated and treated with either the hypoxia-conditioned medium or a normoxic control medium. Cell proliferation and IR-induced cell death were examined to determine the mechanism by which the hAdMSC secretome exerted its effects. RESULTS: The conditioned hAdMSC secretome contained high levels of GM-CSF, VEGF, IL-6, and IGF-1. Repeated systemic infusion with the hAdMSC secretome resulted in improved salivation capacity and increased levels of salivary proteins, including amylase and EGF, relative to the PBS group. The microscopic structural integrity of SG was maintained and salivary epithelial (AQP-5), endothelial (CD31), myoepithelial (α-SMA) and SG progenitor cells (c-Kit) were successfully protected from radiation damage and remodeled. The hAdMSC secretome strongly induced proliferation of HPEC and led to a significant decrease in cell death in vivo and in vitro. Moreover, the anti-apoptotic effects of the hAdMSC secretome were found to be promoted after hypoxia-preconditioning relative to normoxia-cultured hAdMSC secretome. CONCLUSION: These results show that the hAdMSC secretome from hypoxic-conditioned medium may provide radioprotection and tissue remodeling via release of paracrine mediators.