Novel guanidine compounds inhibit platelet-derived growth factor receptor alpha transcription and oligodendrocyte precursor cell proliferation.

Oligodendrocyte precursor cells (OPCs), also known as NG2 cells or polydendrocytes, are distributed widely throughout the developing and mature central nervous system. They remain proliferative throughout life and are an important source of myelinating cells in normal and demyelinating brain as well as a source of glioma, the most common type of primary brain tumor with a poor prognosis. OPC proliferation is dependent on signaling mediated by platelet-derived growth factor (PDGF) AA binding to its alpha receptor (PDGFRα). Here, we describe a group of structurally related compounds characterized by the presence of a basic guanidine group appended to an aromatic core that is effective in specifically repressing the transcription of Pdgfra but not the related beta receptor (Pdgfrb) in OPCs. These compounds specifically and dramatically reduced proliferation of OPCs but not that of astrocytes and did not affect signal transduction by PDGFRα. These findings suggest that the compounds could be further developed for potential use in combinatorial treatment strategies for neoplasms with dysregulated PDGFRα function.

Neighborhood predictors of bullying perpetration and victimization trajectories among South Korean adolescents.

AIMS: This study examined latent trajectories of bullying perpetration and victimization, and identified neighborhood antecedents of these trajectories among South Korean adolescents. METHODS: Nationally representative individual-level data from waves 2 to 6 (middle school to high school) of the Korean Children and Youth Panel Survey were merged with neighborhood-level data drawn from the Korean Census and the Korean Ministry of Education. Latent class growth analysis (N = 2,178) and logistic regression were conducted (N = 2,021). RESULTS: Three unique trajectories of bullying experience-low-risk (80.8%), transient (13.3%), high-risk (5.9%)-were identified. Neighborhood factors (e.g., public assistance receipt, marital status, official bullying incidents, collective efficacy) predicted these distinct developmental paths. CONCLUSION: Joint trajectories of perpetration and victimization can inform service or policy decisions as each developmental path may represent unique experiences for youth in need of specific resources for treatment or intervention. Neighborhood indicators are important predictors of developmental trajectories of bullying experience among adolescents.

Effect of irradiation-induced intercellular adhesion molecule-1 expression on natural killer cell-mediated cytotoxicity toward human cancer cells.

BACKGROUND AIMS: Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. METHODS: Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. RESULTS: LFA-1 expression increased on NK cells after expansion (P <0.001). The expression of ICAM-1 was significantly upregulated by irradiation after 24 h in various cell lines, including HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P <0.001) and U937 (P <0.001), although the level of expression depended on the cell line. ICAM-1 expression was extremely low before and after irradiation in U251 cells. NK cell-mediated cytotoxicity increased after irradiation of HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P = 0.003), and U937 (P = 0.004) cells, in which ICAM-1 expression was significantly increased after irradiation. IFN-γ production by NK cells in response to HL60 (P <0.001) and T47D (P = 0.011) cells significantly increased after irradiation. NK cell-mediated cytotoxicity against irradiated SKBR-3 (P <0.001) and irradiated T47D cells (P = 0.035) significantly decreased after blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced cytotoxicity against irradiated HL60 (P <0.001) and irradiated SKBR-3 (P <0.001). CONCLUSIONS: Irradiation upregulates ICAM-1 expression on the surface of human cancer cells and enhances activated NK cell-mediated cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells.

Correlation of biologically effective dose and the tumor control in Stage I (<5 cm) non-small cell lung cancer with stereotactic ablative radiotherapy: a single institutional cohort study.

BACKGROUNDS: Stereotactic ablative radiotherapy (SABR) is one of the newly developed innovative radiotherapy and of which optimal dose prescription needs to be standardized. We aimed to investigate the dose-response relationship for patients with SABR. METHODS: Fifty-three patients with Stage I non-small cell lung cancer patients, who underwent SABR between November 2006 and January 2015, were evaluated retrospectively. Thirteen patients (24.5%), who refused the surgery were included and 40 patients (75.5%) were medically inoperable at diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3-8 fractions and the median biologically effective dose (BED;α/ß = 10) was 105.6 Gy (range: 60-160.53 Gy). RESULTS: The median follow-up was 37.1 months. The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and progression-free survival rate were 63.3% and 47.5%, respectively, and freedom from progression was 62.2%. Local control rate and 3-year overall survival according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45% in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4% in ≤100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in five (9.4%) patients. CONCLUSIONS: The excellent regional control was conferred with a prescription of more than BED10 of 100 Gy, which also might be needed to achieve better local tumor control in T2a patients with tolerable lung function.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. METHODS: We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. RESULTS: Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). CONCLUSION: Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Confidence limits for patient-specific IMRT dose QA: a multi-institutional study in Korea.

This study aims to investigate tolerance levels for patient-specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi-institutional study. Eleven institutions participated in the multi-institutional study in Korea. A total of 155 DQA measurements, consisting of point-dose differences (high- and low-dose regions) and gamma passing rates (composite and per-field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro-Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two-sided Student's t-distribution were applied to determine the confidence limits for the grouped data. The Spearman's test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t-distributions were negligible for the point-dose data and the gamma passing rates with 3%/3 mm criteria. However, with 2%/2 mm criteria, the difference in CLs were 1.6% and 2.2% for composite and per-field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2 mm. There was no noticeable correlation among the different QA methods. Our multi-institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation.

Blood Lymphocytes as a Prognostic Factor for Stage III Non-Small Cell Lung Cancer with Concurrent Chemoradiation.

We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Direct Tumor Irradiation Potentiates Adoptive NK Cell Targeting Against Parental and Stemlike Cancer in Human Liver Cancer Models.

PURPOSE: Radiation therapy (RT) has been shown to effectively induce the expression of intercellular adhesion molecule-1 (ICAM-1), which is recognized by lymphocyte function-associated antigen 1 (LFA-1) expressed on natural killer (NK) cells. However, the potential synergistic antitumor immune response of tumor irradiation and administered NK cells has not been explored in intractable human liver cancers. Furthermore, NK cell targeting against both parental and cancer stemness has never been investigated. METHODS AND MATERIALS: Highly activated ex vivo NK cells were administered into the human liver tumor-bearing mice. Tumor direct RT was optimized according to tumor bearing site. HepG2 and Hep3B ICAM-1 knockout cells were generated using CRISPR/CAS9. Stemness tumor spheres were generated. NK cell cytolysis against parental and tumor sphere was evaluated using flow cytometry and real-time cytotoxicity assay. RESULTS: A combination of adoptive NK cell therapy with RT significantly improved therapeutic efficacy over monotherapies against subcutaneous, orthotopic, and metastatic human liver tumor models. Direct tumor irradiation potentiated NK cell recognition and conjugation against liver cancer through the LFA-1/ICAM-1 axis. Suppression of immune synapse formation on NK cells using high-affinity LFA-1 inhibitors or ICAM-1 knockout liver cancer induced "outside-in" signal blocking in NK cells, resulting in failure to eliminate liver tumor despite the combination therapy. NK cells effectively recognized and targeted triple-high epithelial cell adhesion molecule+CD133+CD24+ liver cancer expressing upregulated ICAM-1 in the irradiated tumor microenvironment, which led to prevention of the initiation of metastasis, improving survival in a metastatic model. In addition, the LFA-1/ICAM-1 axis interruption between NK cells and stemness liver tumor spheres significantly diminished NK cell cytolysis. Consistent with our preclinical data, the LFA-1/ICAM-1 axis correlated with survival outcomes in patients with metastatic cancer from the The Cancer Genome Atlas databases. CONCLUSIONS: NK cells in combination with tumor irradiation can provide synergistic therapeutic effects for NK cell recognition and elimination against both parental and stemlike liver cancer through LFA-1/ICAM-1.

A multi-institutional study for tolerance and action levels of IMRT dose quality assurance measurements in Korea.

The purpose of this study was to suggest tolerance levels for IMRT DQA measurements using confidence limits determined by a multi-institutional study in Korea. Ten institutions were grouped into LINAC (seven linear accelerators) and TOMO (three tomotherapy machines). The DQA processes consisted of point (high- and low-dose regions) and planar (per-field and composite-field) dose measurements using an ion chamber and films (or 2D detector array) inserted into a custom-made acryl phantom (LINAC) or a cheese phantom (TOMO). The five mock structures developed by AAPM TG-119 were employed, but the prostate as well as the H&N structures were modified according to Korean patients' anatomy. The point measurements were evaluated in a ratio of measured and planned doses, while the planar dose distributions were assessed using two gamma criteria of 2 mm/2% and 3 mm/3%. The confidence limit (|mean + 1.96 σ|) for point measurements was determined to be 3.0% in high-dose regions and 5.0% in low-dose regions. The average percentage of points passing the gamma criteria of 2 mm/2% and 3mm/3% for per-field measurements was 92.7 ± 6.5% and 98.2 ± 2.8%, respectively. Thus, the corresponding confidence limit was 79.1% and 92.7%, respectively. The gamma passing rate averaged over all mock tests and institutions for composite-field measurements was 86.1 ± 6.5% at 2 mm/2% and 95.3 ± 3.8% at 3 mm/3%, leading to the confidence limit of 73.3% and 87.9%, respectively. There was no significant difference in the tolerance levels of point dose measurements between LINAC and TOMO groups. In spite of the differences in mock structures and dosimetry tools, our tolerance levels were comparable to those of AAPM and ESTRO guidelines.

Depression in South Korean Adolescents Captured by Text and Opinion Mining of Social Big Data.

Depression in adolescence is recognized as an important social and public health issue that interferes with continued physical growth and increases the likelihood of other mental disorders. The goal of this study was to examine online documents posted by South Korean adolescents for 3 years through the text and opinion mining of collectable documents in order to capture their depression. The sample for this study was online text-based individual documents that contained depression-related words among adolescents, and these were collected from 215 social media websites in South Korea from 1 January 2012 to 31 December 2014. A sentiment lexicon was developed for adolescent depressive symptoms, and such sentiments were analyzed through opinion mining. The depressive symptoms in the present study were classified into nine categories as suggested by the Diagnostic and Statistical Manual for Mental Disorders, 5th Edition (DSM-5). The association analysis and decision tree analysis of data mining were used to build an efficient prediction model of adolescent depression. Opinion mining indicated that 15.5% were emotionally stable, 58.6% moderately stressed, and 25.9% highly distressed. Data mining revealed that the presence of depressed mood most of the day or nearly every day had the greatest effect on adolescents' depression. Social big data analysis may serve as a viable option for developing a timely response system for emotionally susceptible adolescents. The present study represents one of the first attempts to investigate depression in South Korean adolescents using text and opinion mining from three years of online documents that originally amounted to approximately 3.1 billion documents.

Exploring Future Signals of COVID-19 and Response to Information Diffusion Using Social Media Big Data.

COVID-19 is a respiratory infectious disease that first reported in Wuhan, China, in December 2019. With COVID-19 spreading to patients worldwide, the WHO declared it a pandemic on 11 March 2020. This study collected 1,746,347 tweets from the Korean-language version of Twitter between February and May 2020 to explore future signals of COVID-19 and present response strategies for information diffusion. To explore future signals, we analyzed the term frequency and document frequency of key factors occurring in the tweets, analyzing the degree of visibility and degree of diffusion. Depression, digestive symptoms, inspection, diagnosis kits, and stay home obesity had high frequencies. The increase in the degree of visibility was higher than the median value, indicating that the signal became stronger with time. The degree of visibility of the mean word frequency was high for disinfectant, healthcare, and mask. However, the increase in the degree of visibility was lower than the median value, indicating that the signal grew weaker with time. Infodemic had a higher degree of diffusion mean word frequency. However, the mean degree of diffusion increase rate was lower than the median value, indicating that the signal grew weaker over time. As the general flow of signal progression is latent signal → weak signal → strong signal → strong signal with lower increase rate, it is necessary to obtain active response strategies for stay home, inspection, obesity, digestive symptoms, online shopping, and asymptomatic.

Efficacy of hypofractionated preoperative chemoradiotherapy in rectal cancer.

The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4-8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits.

Randomized, Multicenter, Phase 3 Study of Accelerated Fraction Radiation Therapy With Concomitant Boost to the Gross Tumor Volume Compared With Conventional Fractionation in Concurrent Chemoradiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer: The Korean Radiation Oncology Group 09-03 Trial.

PURPOSE: We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin. RESULTS: The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P = .612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P = .508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P = .295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P = .615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P = .134) or radiation esophagitis (P = .539). CONCLUSIONS: This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy.

Individual- and School-level Predictors of Latent Profiles of Bullying Victimization: Comparing South Korea and the United States.

This cross-national research investigated nationally representative adolescents from South Korea and the United States, explored similarities and differences in latent profiles of bullying victimization between countries, and examined individual- and school-level variables that predict such latent profiles supported by the Social Disorganization Theory. The fourth-grade sample of the 2015 Trends in International Mathematics and Science Study from South Korea (N = 4,669) and the United States (N = 10,029) was used to conduct a latent profile analysis based on eight items of the bullying victimization questionnaire. Multilevel logistic regression was conducted using latent profiles as dependent variables. Independent variables include individual-level (material goods, school absence, academic interest, school belonging) and school-level (concentration of affluent families, school resources, the severity of delinquency, academic commitment) factors. More similarities existed than differences in the latent groups of bullying victimization between South Korea (rare, low-moderate, verbal-relational-physical, and multi-risk) and the United States (rare, low-moderate, verbal-relational, and multi-risk). Evidence for school-level variables as predictors of bullying victimization profiles was stronger for adolescents in the United States, with a concentration of affluent families and severity of delinquency being significant in four of the six models. For the South Korean sample, the severity of delinquency predicted bullying victimization in only one model. Examination of both individual- and school-level factors that predict unique bullying victimization experiences grounded in Social Disorganization Theory may be informative for addressing key areas of intervention-especially at the school-level context in which victimization primarily takes place and where anti-bullying intervention programs are often provided.

PIVKA-II as a surrogate marker for prognosis in patients with localized hepatocellular carcinoma receiving stereotactic body radiotherapy.

PURPOSE: This study aimed to determine the correlation between protein induced by vitamin K absence or antagonist-II (PIVKA-II) and stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Sixty-one patients received SBRT between 2015 and 2020 with a median dose of 48 Gy (range, 39 to 60 Gy) with a median of 4 fractions. Changes in tumor markers before and after SBRT were analyzed. RESULTS: The median follow-up period was 31 months (range, 12 to 64 months). The estimated 2-year in-field failure-free survival, progression-free survival (PFS), and overall survival rates were 82.0%, 39.3%, and 96.7%, respectively. Patients with decreased PIVKA-II levels through SBRT had significantly few in-field failures (p = 0.005). Patients with PIVKA-II levels of ≤25 mAU/mL after SBRT had significantly long PFS (p = 0.004). CONCLUSION: PIVKA-II could be a useful surrogate marker for response or survival outcomes in patients with localized HCC receiving SBRT.

Metabolic response of pelvic and para-aortic lymph nodes during radiotherapy for carcinoma of the uterine cervix: using positron emission tomography/computed tomography.

OBJECTIVES: We evaluated the metabolic response of lymph nodes (LNs) using consecutive F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and correlated the metabolic response with the volumetric response measured by consecutive CT. METHODS: Twenty-two patients with cervical cancer that had positive LNs underwent preradiotherapy (pre-RT) and inter-RT PET/CT. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value. All patients underwent inter-RT CT simulation after 45 Gy to the whole pelvis and inter-RT PET/CT scans after median 63 Gy to the gross LNs. RESULTS: A total of 48 pelvic and para-aortic LNs were found on the pre-RT PET/CT. The mean maximal standardized uptake value of nodal disease decreased from the pre-RT of 5.2 (SD, 3.1; range, 1.8-15.6) to the inter-RT of 1.1 (SD, 2.1; range, 0-11.1). Classifying the metabolic response of all 48 nodal lesions on the inter-RT PET/CT, 38 had a complete metabolic response. The initial volume of LNs had no correlation with the metabolic response (r = 0.194, P = 0.186). The metabolic response between the pre-RT PET/CT and inter-RT PET/CT was significantly associated with the volume response between the pre-RT CT and inter-RT CT (r = 0.314, P < 0.05). However, 18 (38%) LNs showed discrepancy between metabolic response and residual LN volume. Six (27%) patients had modified RT during treatment based on inter-RT PET/CT. CONCLUSIONS: We suggest that the PET/CT can be a useful tool for the evaluation of the interim response of the LNs and aid in selecting patients that need further treatment. The results showed a significant correlation between the metabolic and volumetric responses during RT, although the anatomical changes of LNs would not always represent the metabolic status.

VEGF as a predictor for response to definitive chemoradiotherapy and COX-2 as a prognosticator for survival in esophageal squamous cell carcinoma.

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.

Favorable prognosis of patients who received adjuvant androgen deprivation therapy after radiotherapy achieving undetectable levels of prostate-specific antigen in high- or very high-risk prostate cancer.

INTRODUCTION: To determine the prognostic significance of long-term adjuvant androgen deprivation therapy (A-ADT) over 1 year in achieving undetectable levels of prostate-specific antigen (PSA) less than 0.001 ng/mL in prostate cancer patients with high- or very high-risk prostate cancer who underwent radiotherapy (RT). MATERIALS AND METHODS: A total of 197 patients with prostate cancer received RT, with a follow-up of ≥12 months. Biochemical failure was defined as PSA ≥nadir + 2 ng/mL after RT. We analyzed clinical outcomes, including survival, failure patterns, and prognostic factors affecting outcomes. RESULTS: Biochemical failure-free survival (BCFFS), clinical failure-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival (OS) rates at 5 years were 91.1%, 95.4%, 96.9%, 99.5%, and 89.1%, respectively. Administration of long-term A-ADT significantly predicted favorable BCFFS (p = 0.027) and OS (p < 0.001) in multivariate analysis. Nadir PSA ≤0.001 ng/mL was an independent prognostic factor for BCFFS (p = 0.006) and OS (p = 0.021). The use of long-term A-ADT significantly affected nadir PSA ≤0.001 ng/mL (p < 0.001). The patients with A-ADT for 1 year or longer had better BCFFS or OS than those for less than 1 year or those without A-ADT (p < 0.001). The best prognosis was demonstrated in patients treated with long-term A-ADT and nadir PSA ≤0.001 ng/mL in BCFFS (p < 0.001). CONCLUSION: The addition of long-term A-ADT over 1 year to RT demonstrated good treatment outcomes in patients with locally advanced prostate cancer. Achieving a nadir PSA value ≤0.001 ng/mL using combination therapy with RT and A-ADT is a powerful clinical predictor of treatment outcomes.

A dummy-run evaluation of postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trials for cervical cancer.

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.

Treatment time to the end of thoracic radiotherapy has more predictive power for survival than radiation dose intensity in patients with limited-stage small-cell lung cancer receiving concurrent chemoradiation of more than 45 Gy.

The optimal protocol for thoracic radiotherapy (TRT) in combination with chemotherapy in patients with limited-stage small-cell lung cancer (LS-SCLC) remains elusive. The present study aimed to evaluate radiation parameters in association with survival outcomes. A total of 101 patients with LS-SCLC who completed TRT at ≥45 Gy and concurrent chemotherapy were retrospectively reviewed. The median dose and duration of TRT were 50 Gy and 38 days, respectively. The median duration from the start of either therapy to the end of TRT (SER) was 60 days. The median survival for all patients was 26.9 months. The 3-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 52.0, 29.5 and 37.6%, respectively, and the 5-year LC, PFS and OS rates were 50.1, 28.3 and 26.7%, respectively. Univariate analysis revealed that patient age, tumor stage, timing and dose of TRT, SER, prophylactic cranial irradiation (PCI), and tumor response were significantly associated with treatment outcomes. Multivariate analysis revealed that stage was the only significant prognostic factor for LC (P=0.011), PFS (P<0.001) and OS (P<0.001). Tumor response (P=0.014), PCI (P=0.007) and SER (P=0.005) were significant predictors of OS. OS was improved in patients who achieved complete response, and their SER was ≤70 days (P<0.001). Short treatment duration (SER ≤70 days) was a significant predictor of OS in patients with LS-SCLC who completed planned TRT at ≥45 Gy with concurrent chemoradiotherapy.