Analysis of lithotripsy efficiency and stone retropulsion displacement according to pulse characteristics of Ho: YAG laser with Moses effect.

BACKGROUND AND OBJECTIVES: Compared to the conventional Ho: YAG laser, a Ho: YAG laser device has been reported that has a Moses effect to reduce stone retropulsion and increase lithotripsy efficiency. The principle of this equipment is to convert a single laser pulse into two pulses. Most studies on such lasers are limited to lithotripsy efficiency and the prevention of stone retropulsion; studies according to each pulse condition have not been performed. Therefore, the purpose of this study was to quantify the bubble shape, lithotripsy efficiency, and stone retropulsion displacement in a ureteral phantom according to the modulation of the first pulse characteristics of the Moses effect laser under conditions that maintained the total energy and repetition rate. MATERIAL AND METHODS: In this study, a Ho: YAG laser system (Holinwon Pro, Wontech Inc., Korea) with an emission wavelength of 2.10 µm and a Moses effect was used. To verify the Moses effect based on the changes in the pulse, a water tank was fabricated, and the ureteral phantom was manufactured in a structure that could be easily installed in the water tank. Additionally, a spherical artificial stone in the ureteral phantom was prepared by mixing calcined gypsum (Cacinated Gypsum) and water at a ratio of 3:1. In the ureteral phantom, a high-speed camera (FASTCAM NOVA S12, Photron Inc.) and visible light were used to record pulse-dependent image analysis of bubbles and stone retropulsion. RESULT: After mounting the artificial stone in the ureteral phantom, the pulse duration and energy of the first pulse of the Moses effect laser were varied; 30 laser shots for 3 s at a repetition rate of 10 Hz were applied to quantify the lithotripsy efficiency and stone retropulsion displacement, and the experimental values were compared. The fragmentation efficiency was confirmed by measuring the mass before and after the laser pulse application, the original position of the stone retropulsion displacement, and the distance moved. The minimum value of stone retropulsion displacement appeared when the pulse duration of the first pulse was 300 µs, the pulse energy was 100 mJ, and the value was approximately 0.28 mm. The highest fragmentation efficiency was observed under the same conditions, and the mass loss of the artificial stone at that time was approximately 3.7 mg. CONCLUSION: Quantitative indices, such as lithotripsy efficiency and stone retropulsion displacement, were confirmed using ultrahigh-speed cameras to determine the effect of the first pulse energy and duration of the Ho: YAG laser with the Moses effect on stone removal. It was confirmed that the longer the duration of the primary pulse and the lower the energy, the higher the fragmentation efficiency. In this study, the possibility of manufacturing a laser with an optimal stone-removal effect was confirmed according to the first-pulse condition of the laser with the Moses effect.

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-ß (Aß) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. OBJECTIVE: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. METHODS: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aß42/Aß40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. CONCLUSIONS: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.

The effects of low-dose radiation therapy in patients with mild-to-moderate Alzheimer's dementia: an interim analysis of a pilot study.

PURPOSE: We aimed to determine whether low-dose radiotherapy (LDRT) is effective in patients with Alzheimer disease (AD). MATERIALS AND METHODS: We included patients according to the following criteria: probable Alzheimer's dementia according to the New Diagnostic Criteria for Alzheimer's Disease; confirmation of amyloid plaque deposits on baseline amyloid positron emission tomography (PET); a Korean Mini-Mental State Examination 2nd edition (K-MMSE-2) score of 13-26; and a Global Clinical Dementia Rating (CDR) score of 0.5-2 points. LDRT was performed six times at 0.5 Gy each. Post-treatment cognitive function tests and PET-CT examinations were performed to evaluate efficacy. The medication for AD treatment was maintained throughout the study period. RESULTS: At 6 months after LDRT, neurological improvement was seen in 20% of patients. Patient #2 showed improvement in all domains of the Seoul Neuropsychological Screening Battery II (SNSB-II). Moreover, the K-MMSE-2 and Geriatric Depression Score-Short Form scores improved from 20 to 23 and from 8 to 2, respectively. For patient #3, the CDR score (sum of box score) improved from 1 (4.0) to 1 (3.5) at 3 months follow-up. Moreover, the Z scores for language and related functions, memory, and frontal executive function improved to -2.56, -1.86, and -1.32, respectively at the 6-month follow-up. Two patients complained of mild nausea and mild hair loss during LDRT, which improved after treatment. CONCLUSION: One of the five patients with AD treated with LDRT experienced a temporary improvement in SNSB-II. LDRT is tolerable in patients with AD. We are currently under follow-up and will conduct cognitive function tests after 12 months after LDRT. A large-scale randomized controlled trial with a longer follow-up period is warranted to determine the effect of LDRT on patients with AD.

Effect of fermentation on antioxidant, antimicrobial, anti-inflammatory, and anti-Helicobacter pylori adhesion activity of Ulmus davidiana var. japonica root bark.

The limited yield of Ulmus davidiana var. japonica root bark (URB) extract is considered an economic loss to the food industry. Improving extraction yield and bioactivity through fermentation increase the industrial usage of URB. The study aims to optimize the fermentation with cellulolytic and pectinolytic bacteria and evaluate the bioactivity and anti-Helicobacter pylori activity of the fermented URB extract. URB fermentation with the Bacillus licheniformis FLa3, isolated from salted seafood (Sardinella zunasi), under optimal conditions (37 °C, pH 6, 10% inoculum dose, and 36 h) improved the extraction yield by 36% compared to the control. The antioxidant and antimicrobial activity of the fermented extract were significantly higher than non-fermented extract. High-performance liquid chromatography results confirmed that the fermentation increased the proportion of bioactive components such as catechin (171.7%), epicatechin (144.3%), quercetin (27.3%), and kaempferol (16.7%). The results confirmed that the fermentation increased both the extraction yield and bioactivity.

Fused toes homolog, a potential molecular regulator of human papillomavirus type 16 E6 and E7 oncoproteins in cervical cancer.

Human papillomavirus type 16 (HPV16) plays a major role in the development of cervical cancer. The oncogenic potential of HPV16 is attributed to E6 and E7 oncoproteins. Here, we investigated the relationship between fused toes homolog (FTS) and HPV16 E6 and E7 in cervical cancer cells. HPV16-positive CaSki and SiHa cell lines were used for in vitro studies. FTS silencing was performed using a small interfering RNA (siRNA)-based approach, and western blotting was performed to determine the protein expression of tumor suppressors and cell survival markers. Immunoprecipitation, immunofluorescence, in silico analysis, and immunohistochemistry were performed to determine the interaction between, and intracellular co-localization of, FTS and both the E6 and E7 proteins. Silencing of FTS reduced the expression of the E6 and E7 proteins in cervical cancer cell lines and conversely increased the expression of the tumor suppressor proteins p53 and retinoblastoma protein. However, the primary transcripts of HPV16 E6 and E7 were unaffected by FTS silencing; furthermore, FTS transcription was unaffected by silencing of either E6 or E7, suggesting their interaction occurs post-translationally. Immunofluorescence and immunohistochemistry analysis demonstrated co-localization of FTS with the HPV16 E6 and E7 proteins, while immunoprecipitation results suggested that FTS interacts with both E6 and E7. Furthermore, in silico structural analysis identified putative residues involved in the binding of FTS with E6 and E7. Taken together, these results show that FTS affects both HPV16 E6 and E7 oncogenes in cervical cancer. We propose FTS as a target for the prevention of cervical cancer development and progression.

Virtual randomized study comparing lobectomy and particle beam therapy for clinical stage IA non-small cell lung cancer in operable patients.

To the best of our knowledge there have been no randomized controlled trials comparing lobectomy-a standard treatment for patients with early-stage non-small cell lung cancer (NSCLC)-and particle beam therapy (PBT), the best performing existing radiotherapy. We conducted a virtual randomized trial in medically operable patients with stage IA NSCLC to compare lobectomy and PBT effectiveness. A Markov model was developed to predict life expectancy after lobectomy and PBT in a cohort of patients with stage IA NSCLC. Ten thousand virtual patients were randomly assigned to each group. Sensitivity analyses were performed as model variables and scenarios changed to determine which treatment strategy was best for improving life expectancy. All estimated model parameters were determined using variables extracted from a systematic literature review of previously published articles. The preferred strategy differed depending on patient age. In young patients, lobectomy showed better life expectancy than that of PBT. The difference in life expectancy between lobectomy and PBT was statistically insignificant in older patients. Our model predicted lobectomy as the preferred strategy when operative mortality was under 5%. However, the preferred strategy changed to PBT if operative mortality post lobectomy was over 5%. For medically operable patients with stage IA NSCLC, our Markov model revealed the preferred strategy of lobectomy or PBT regarding operative mortality changed with varying age and comorbidity. Until randomized controlled trial results become available, we hope the current results will provide a rationale background for clinicians to decide treatment modalities for patients with stage IA NSCLC.

Modulation of Neuroinflammation by Low-Dose Radiation Therapy in an Animal Model of Alzheimer's Disease.

PURPOSE: Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflammatory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT may be used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have not been determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investigate the therapeutic effects and mechanisms of low-dose RT in AD. METHODS AND MATERIALS: We first determined the proper dose and schedule for RT in late-stage AD using 8- to 9-month-old 5x Familial AD (5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with low dose per fraction (LD-LDRT, 5 × 0.6 Gy) with those of a low moderate total dose with conventional dose per fraction (LMD-CDRT, 5 × 2 Gy). RESULTS: LD-LDRT and LMD-CDRT were found to reduce the levels of the proinflammatory cytokines CD54, IL-3, CXCL9/10, and CCL2/4 in the hippocampus of 5xFAD mice. Furthermore, increased microgliosis assessed using Iba-1 and CD68 dual immunostaining was significantly reduced by LD-LDRT and LMD-CDRT in the hippocampus of 5xFAD mice. Moreover, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in the hippocampus of 5xFAD mice and attenuated their cognitive impairment; these effects persisted for 4 to 5 weeks. CONCLUSIONS: The present study showed that LD-LDRT alleviates cognitive impairments and prevents the accumulation of amyloid plaques by regulating neuroinflammation in the late stage of AD in 5xFAD mice, with an efficacy equivalent to that of LMD-CDRT. Furthermore, the findings suggest that compared with LMD-CDRT, LD-LDRT may facilitate accessible and convenient treatment in clinical trials.

Indocyanine green-loaded injectable alginate hydrogel as a marker for precision cancer surgery.

BACKGROUND: Accurate identification of tumor sites and boundaries is of paramount importance during minimally invasive surgery. Although laparoscopic resection is being increasingly and widely performed for early gastric and colorectal cancers, the detection of tumors located inside the stomach and intestine is difficult owing to the lack of tactile sensation. Here, we propose the application of an indocyanine green (ICG)-loaded alginate hydrogel system as a fluorescence surgical marker for precise laparoscopic operations. METHODS: A physical complex of ICG and human serum albumin (HSA) was mixed with sodium alginate to form an injectable hydrogel system. Calcium carbonate and D-gluconic acid (GA) were added to the gel to control its strength and gelation time, respectively. The optimal conditions for the preparation of injectable hydrogels were determined by analyzing the fluorescence spectra and sol-gel transition time of the prepared samples at various concentrations and compositions. Next, the aqueous solutions of ICG, ICG-HSA, and ICG-HSA-loaded alginate were subcutaneously injected into nude mice (three mice per group), and near-infrared (NIR) fluorescence images of the mice (λex. =780 nm, λem. =845 nm) were obtained at different points in time for 8 days. Then, fluorescence intensities at the injection sites, target-to-background ratio, and areas of ICG fluorescence were analyzed. Finally, the potential utility of ICG-HSA-loaded alginate hydrogel as a surgical marker was evaluated in a porcine model. The ICG-HSA-loaded alginate solution was injected into three sites in the submucosal space of the porcine stomach via a catheter. A fluorescent laparoscopic system was installed on the abdomen of the pig 3 days post-injection, and the fluorescence signal generated from the fluorescence surgical marker located inside the stomach was evaluated using the fluorescence laparoscope system (λex. =785 nm, λem. =805 nm). RESULTS: The optimal concentration of ICG-HSA complex was determined to be 30 µM, and maximum fluorescence intensity of the complex was obtained at a 1:1 mole ratio of HSA to ICG. The subcutaneous injection of ICG or ICG-HSA solution in mice resulted in the rapid spread of the fluorescence signal around the injection site in 3 h, and a weak fluorescence was detected at the injection site 24 h post-injection. In contrast, the fluorescence detection time was effectively prolonged up to 96 h post-injection in the case of ICG-HSA-loaded alginate gel, while diffusion of the injected ICG from the injection site was effectively prevented. In the laparoscopic operation, injection sites of the hydrogel in porcine stomach could be accurately detected in real time even after 3 days. CONCLUSIONS: This alginate hydrogel system may be potentially useful as an effective surgical marker in terms of accuracy and persistence for laparoscopic operation.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer.

PURPOSE: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). MATERIALS AND METHODS: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. RESULTS: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). CONCLUSION: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended.

Lobectomy versus stereotactic ablative radiotherapy for medically operable patients with stage IA non-small cell lung cancer: A virtual randomized phase III trial stratified by age.

BACKGROUND: Although the choice between stereotactic ablative radiotherapy (SABR) and lobectomy for early-stage non-small cell lung cancer (NSCLC) has been debated for years, the two procedures have not yet been directly compared in a randomized trial. We conducted a virtual randomized phase III trial stratified by age to compare the effectiveness of lobectomy and SABR for medically operable patients with stage IA (AJCC eighth) NSCLC using the Markov model analysis. METHODS: A Markov model was developed to simulate a cohort of patients aged 45-85 years with stage IA NSCLC who had undergone either lobectomy or SABR and were followed up for their remaining lifetime. Each virtual patient was randomly assigned to undergo lobectomy or SABR, and 10 000 patients were allocated to each group. All estimates of the variables were obtained by a systematic review of published articles. RESULTS: The lobectomy group showed a better life expectancy than the SABR group, in patients under 75 years of age. However, no statistically significant difference was seen in patients 75 years or older. The predicted life expectancy was 9.43 and 8.70 years in 75-year-old patients in the lobectomy and SABR groups, respectively. However, the 95%CI for the difference in life expectancy between the two groups was - 0.06-1.50 years (P = 0.0689). CONCLUSIONS: The Markov model showed no statistically significant difference in the expected overall survival in stage IA NSCLC patients who were older than 75 years and had undergone SABR or lobectomy.

Feasibility of using stereotactic body radiation therapy for unresectable soft tissue tumors of the trunk.

PURPOSE: To evaluate the feasibility of stereotactic body radiation therapy (SBRT) for unresectable soft tissue tumors of the trunk. MATERIALS AND METHODS: Between January 2002 and December 2008, 23 patients with 36 lesions of soft tissue tumors, which were located in the trunk and not suitable for resection, underwent SBRT. Among the 36 lesions, 31 were malignant and 5 were benign. The median tumor volume was 24 cm3 (range, 2.6-213 cm3). SBRT doses ranged from 20 to 48 Gy in 1-5 fractions. RESULTS: With a median follow-up of 73 months, the overall survival (OS) and local control (LC) rates at 5 years were 39% and 52%, respectively. For malignant tumors, the OS and LC rates at 5 years were 28% and 47%, respectively. For benign tumors, the OS and LC rates at 5 years were 80% and 100%, respectively. There was no acute toxicity of grade ≥3. One case of grade 3 late skin toxicity was reported 10 months after SBRT. CONCLUSION: SBRT may be an effective and safe treatment modality for the local control of unresectable soft tissue tumors of the trunk including tumors of a benign nature.

Estimation of the medical need for carbon-ion radiotherapy in Korea.

The Korea Heavy Ion Medical Accelerator project focuses on the development of medical accelerator facilities for delivering carbon-ion beams to cancer patients. The purpose of the present study was to estimate the clinical need for carbon-ion therapy in Korea. Seven tumor sites, namely head and neck, liver, lung, colon and rectum, prostate, bone and soft tissue, and pancreas were selected as eligible sites for receiving carbon-ion radiotherapy (RT) by radiation oncologists of the Korea Institute of Radiological and Medical Sciences. Cancer incidence data for the selected tumor sites were obtained from the Korea National Cancer Incidence Database in order to estimate the potential medical need for carbon-ion RT. The carbon-ion RT adaption rate was assessed based on the clinical experience of other carbon-ion therapy facilities. An estimation model was constructed for estimating the medical need for carbon-ion RT, and from this, 25 606 patients were deemed to be potential candidates for carbon-ion RT. This estimated potential need corresponded to 10% of newly diagnosed cancer patients in Korea. The realistic estimation was calculated as ranging between 4000 and 6300 patients, depending on the carbon-ion RT adaptation rate. This estimated medical need corresponded to 2-3% of newly diagnosed cancer patients in Korea. Taken together, our findings suggest that there is a clear medical need for carbon-ion RT in Korea, with at least 4000 potential patients per year.

Feasibility of split-course stereotactic ablative radiotherapy for oligometastases.

BACKGROUND: There is growing interest in the use of stereotactic ablative radiotherapy (SABR) for oligometastases. However, extreme caution should be exercised in treating tumors closely located to organs at risk (OARs) with SABR. To reduce complications, we have applied split-course SABR to oligometastases closely located to OARs or to those being retreated with radiotherapy. METHODS: We retrospectively reviewed the records of patients with oligometastases who were treated with planned split-course SABR between January 2012 and December 2016. RESULTS: A total of 23 patients with 29 oligometastatic lesions were enrolled. The primary diagnoses were bone and soft tissue cancers in 13 lesions, liver cancers in 12 lesions, and colorectal cancers in four lesions. The median tumor volume was 78 cm3 (range, 4-1781 cm3). The lesions were treated with 1-3 fractions in the first stage of SABR (first SABR), and one or two fractions in the second stage of SABR (second SABR). The time interval between the two stages was about 4 weeks. A partial response was noted in 16 lesions (55%) after the first SABR, and practical reductions in the doses to OARs were observed in the second SABR compared with the first SABR. The 1-, 2- and 3-year local control rates were 92%, 65% and 43%, respectively. No Grade 4 or 5 toxicities were observed during or after treatment. CONCLUSION: Split-course SABR appeared to be feasible for the treatment of oligometastases closely located to OARs.

Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour model.

Colorectal cancer is one of the leading causes of cancer-related deaths. Although several therapeutic management strategies are available at the early colon cancer stages, such as endoscopic mucosal or submucosal dissection, associated complications often include bleeding or bowel perforations. As an alternative approach, we investigated endoscopic non-ablative fractional laser (eNAFL) irradiation as a minimally invasive therapeutic modality for the treatment of early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse model and demonstrated the early-stage tumour growth delay following the eNAFL irradiation. Additionally, we evaluated the temperature changes in the eNAFL-irradiated area using numerical simulations, and induced inflammation using histological analysis. Our results indicate a minimal thermal damage confined to the irradiated spot, sparing the adjacent tissue and alteration in the tumour microenvironment. eNAFL irradiation may be clinically useful as a minimally invasive therapeutic intervention at the early stage of tumourigenesis. In future, an optimal eNAFL therapeutic dose should be determined, in order to increase the efficacy of this approach.

The Clinical Utilization of Radiation Therapy in Korea between 2011 and 2015.

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2011 and 2015. MATERIALS AND METHODS: We analyzed the claims data from the Health Insurance Review and Assessment Service to estimate the clinical utilization of RT. The source population consisted of all patients who had any of the International Classification of Diseases 10th revision cancer diagnoses (C00-C97) and those with diagnostic codes D00-D48, who were also associated with at least one of the procedure codes related to RT. RESULTS: The total number of patients who received RT in 2011, 2012, 2013, 2014, and 2015 were 54,810, 59,435, 61,839, 64,062, and 66,183, respectively. Among them, the total numbers of male and female patients were 24,946/29,864 in 2011, 27,211/32,224 in 2012, 28,111/33,728 in 2013, 29,312/34,750 in 2014, and 30,266/35,917 in 2015. The utilization rate of RT in cancer patients has also increased steadily over the same period from 25% to 30%. The five cancers that were most frequently treated with RT between 2011 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. More than half of cancer patients (64%) were treated with RT in the capital area (Seoul, Gyeonggi, and Incheon). CONCLUSION: The total number of patients who underwent RT increased steadily from 2011 to 2015 in Korea. The utilization rate of RT in cancer patients is also increasing.

Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors.

PURPOSE: To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. MATERIALS AND METHODS: Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3-4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1-2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. CONCLUSION: SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

BACKGROUND: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection. RESULTS: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047). MATERIALS AND METHODS: Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival. CONCLUSIONS: This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.

Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study.

PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection.

Radiofrequency ablation versus stereotactic body radiotherapy for small hepatocellular carcinoma: a Markov model-based analysis.

The aim of this study is to compare radiofrequency ablation (RFA) with stereotactic body radiotherapy (SBRT) for hepatocellular carcinomas (HCC) smaller than 3 cm. A Markov cohort model was developed to simulate a cohort of patients aged 60-65 years with small HCCs who had undergone either RFA or SBRT and were followed up over their remaining life expectancy. The inclusion criteria were: (1) HCC ≤3 cm in diameter with ≤ 3 nodules; (2) absence of extrahepatic metastasis or portal/hepatic vein invasion; (3) Child-Pugh Class A or B. Twenty thousand virtual patients were randomly assigned to undergo RFA or SBRT. Predicted life expectancy was 6.452 and 6.371 years in the RFA and SBRT groups, respectively. The probability distributions of the expected overall survival were nearly identical. The 95% confidence intervals were 6.25-6.66 and 6.17-6.58 years for RFA and SBRT, respectively. The difference between RFA and SBRT was insignificant (P = 0.2884). Two-way sensitivity analysis demonstrated that if the tumor is 2-3 cm, SBRT is the preferred treatment option. Our Markov model has shown that expected overall survival of SBRT is nearly identical to RFA in HCCs smaller than 3 cm, but SBRT may have an advantage for tumors 2 cm and larger. A randomized trial is required to confirm these findings.

The clinical utilization of radiation therapy in Korea between 2009 and 2013.

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2009 and 2013. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service. The subjects were patients who had diagnostic codes C00-C97 or D00-D48 according to the 10th revision of the International Classification of Diseases, with procedure codes indicating RT treatment. RESULTS: The total number of patients who received RT in 2009, 2010, 2011, 2012, and 2013 were 45,571, 49,593, 54,671, 59,172, and 61,485, respectively. Among them, the total numbers of male and female patients were 20,780/24,791 in 2009, 22,711/26,882 in 2010, 24,872/29,799 in 2011, 27,101/32,071 in 2012, and 27,941/33,544 in 2013. The five cancers that were most frequently treated with RT between 2009 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. The three leading types of cancer among the male patients were lung, colorectal, and liver cancers, whereas in female patients, they were breast, uterine cervical, and lung cancers. The type of cancer most commonly treated by RT was cancer of the central nervous system in patients aged 20 years or less, breast cancer in patients aged 30-50 years, and lung cancer in patients aged 60 years or more. CONCLUSION: Data from this study provided the clinical utilization of RT in Korea between 2009 and 2013.