Predictors of Glaucomatous Progression in Individuals with Small and Large Optic Discs.

PURPOSE: To identify factors associated with glaucomatous progression in individuals with small and large optic discs. DESIGN: Retrospective review. SUBJECTS: 4505 individuals with glaucoma at UCLA; 233 (59.7%) with small discs, 157 (40.3%) with large discs. METHODS: Small and large disc sizes were defined by OCT or Heidelberg Retinal Tomography as disc area ≤ 5% (≤ 1.3 mm2) and ≥ 95% (≥ 2.9 mm2), respectively. Medical records were reviewed for demographics, systemic comorbidities, glaucoma type, ocular comorbidities, and ocular surgery. Logistic regression was used to identify predictors of visual field (VF) progression in individuals with small and large discs and predictors of large versus small discs. MAIN OUTCOME MEASURES: The VF deterioration with mean deviation, pointwise linear regression, and glaucoma rate index (GRI); large vs. small disc. RESULTS: In individuals with small discs, Asian versus non-Hispanic White ethnicity was associated with increased progression (adjusted odds ratio [aOR] = 4.05; 95% confidence interval [CI] = 1.12-14.59 for GRI). Higher intraocular pressure (IOP) range and peak were associated with increased progression in individuals with both small discs (aOR = 1.12; 95% CI = 1.00-1.27 and aOR = 1.05; 95% CI = 1.00-1.10 per 1 mmHg for range and peak with GRI) and large discs (aOR = 1.35; 95% CI = 1.12-1.66 and aOR = 1.11; 95% CI = 1.03-1.20 per 1 mmHg for range and peak with GRI). Multivariable predictors of having large vs. small discs included vasospastic phenotype (aOR = 2.58; 95% CI = 1.35-5.19) and Black (aOR = 20.46; 95% CI = 8.33-61.84), Hispanic/Latino (aOR = 9.65; 95% CI = 4.14-25.39), Asian (aOR = 4.87; 95% CI = 2.96-8.1), and other (aOR = 2.79; 95% CI = 1.69-4.63) versus non-Hispanic White ethnicity. CONCLUSIONS: Increased odds of glaucomatous progression were associated with Asian vs. non-Hispanic White ethnicity in glaucoma patients with small optic discs, as well as with increased IOP range and peak in those with small and large discs. Individuals with a vasospastic phenotype and those from racial and ethnic minority backgrounds had increased odds of having large vs. small optic discs. Further characterization of discernible phenotypes would improve disease prognostication and help individualize glaucoma treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Reading fluency as the bridge between decoding and reading comprehension in Chinese children.

Purpose: Reading fluency has been considered an essential component of reading comprehension, but it is yet to be examined in a reading model in a non-alphabetic writing system. This study investigated whether reading fluency could be identified as a separate construct from decoding and examined the unique role of reading fluency in the Simple View of Reading (SVR). Method: A total of 342 Cantonese-speaking Chinese children in grades 3-5 were recruited to participate in the study. They were assessed on word reading accuracy and fluency, morphological awareness, vocabulary knowledge, and reading comprehension. Results: The confirmatory factor analysis results confirmed that reading fluency is a separate factor from decoding, linguistic comprehension, and reading comprehension. Furthermore, the structural equation modeling results revealed that reading fluency is a significant predictor of reading comprehension and a mediator between decoding and reading comprehension in the extended SVR model. Conclusion: The findings extended previous research in alphabetic languages and supported reading fluency as the bridge between decoding and reading comprehension. The present study highlighted the importance of reading fluency in Chinese reading acquisition in a theoretical framework.

Predicting the developmental trajectories of Chinese reading, English reading, and mathematics: Evidence from Hong Kong Chinese children.

We examined the developmental trajectories and cognitive predictors of first language Chinese reading, second language English reading, and mathematics skills in Hong Kong children in Grades 1-5. We used longitudinal data of 1,000 children (Mage = 7.59 years) assessed on phonological awareness, rapid naming, and morphological awareness in Grade 1 and Chinese word reading, English word reading, and arithmetic calculations in Grades 1-5. Results revealed a decelerating growth pattern for word reading in Chinese and English and a linear growth pattern for arithmetic calculations. Rapid naming and morphological awareness predicted the initial status of all academic skills. The findings suggest that although these academic skills share initial cognitive processes, they follow remarkably different developmental trajectories. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nonattachment mediates the associations between mindfulness, well-being, and psychological distress: A meta-analytic structural equation modeling approach.

Research on nonattachment, a Buddhist psychological construct closely related to mindfulness, has burgeoned since the development of the Nonattachment Scale. The aim of the current meta-analysis was to investigate the mediating role of nonattachment in the relationship between mindfulness and well-being and psychological distress using a meta-analytic structural equation modeling approach. The respective associations of nonattachment and mindfulness with well-being and psychological distress, after controlling for each other, were also examined. Forty-one independent cross-sectional data sets with 24,704 individuals were coded. Results showed that nonattachment partially mediated the associations between mindfulness and well-being and psychological distress. Nonattachment and mindfulness were both significantly positively associated with well-being and negatively associated with psychological distress after controlling for each other. Given the present findings were based on cross-sectional data, more studies with rigorous research design, such as longitudinal, experimental, and intervention studies, should be conducted to further investigate the mediating effect of nonattachment between mindfulness with well-being and distress outcomes and establish causal relations between them. Future research directions regarding nonattachment and its application in mindfulness-based interventions were discussed.

A Web-Based Stratified Stepped Care Mental Health Platform (TourHeart): Semistructured Interviews With Stakeholders.

BACKGROUND: TourHeart, a web-based stratified stepped care mental health platform, is a one-stop solution that integrates psychoeducation and other well-being promotional tools for mental health promotion and mental illness prevention and evidence-based, low-intensity psychological interventions for the treatment of people with anxiety and depressive symptoms. Instead of focusing only on symptom reduction, the platform aims to be person-centered and recovery-oriented, and continual feedback from stakeholders is sought. Understanding the perspectives of users and service providers enables platform developers to fine-tune both the design and content of the services for enhanced service personalization and personal recovery. OBJECTIVE: This qualitative study evaluated a web-based mental health platform by incorporating the perspectives of both users and service providers who administered the platform and provided coaching services. The platform included both web-based and offline services targeting adults along the mental health spectrum based on the two-continua model of mental health and mental illness. METHODS: Interview questions were designed based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework (RE-AIM). Views on offline services, the design of the web-based platform, user experience, and the contents of the platform were explored using semistructured interviews. A total of 27 service users and 22 service providers were recruited using purposive criterion sampling. A hybrid thematic analysis was performed to identify salient aspects of users' and providers' experiences with and views of the platform. RESULTS: Totally, 3 broad themes (namely, the quality of the platform, drivers for platform use, and coaching services) emerged from the interview data that highlighted users' views of and experiences with the web-based platform. The platform's general esthetics, operations, and contents were found to be critical features and drivers for continued use. Although coaching services were indispensable, participants preferred the autonomy and anonymity associated with web-based mental health services. CONCLUSIONS: This study highlights the importance of web-based mental health services being easy to navigate and understand, being user-centric, and providing adequate guidance in self-help. It also confirms existing design standards and recommendations and suggests that more rigorous, iterative user experience research and robust evaluation should be conducted in the future adaptation of web-based stratified stepped care services, so that they can be more personalized and better promote personal recovery.

Executive functions in Chinese kindergarten children with early reading problems.

Learning to read Chinese is a complex task that draws on a range of executive function (EF) skills since early development. However, no studies have examined EF as a potential contributing factor to early reading problems among Chinese children. The present longitudinal study identified 48 poor readers and 48 normal readers among a sample of 190 Chinese children at the end of kindergarten. Measures of EF skills (working memory, inhibition control, and cognitive flexibility) and reading outcomes (word reading, sentence reading fluency, and sentence reading comprehension) were administered to the children. The two groups were retrospectively compared on the EF measures after age and nonverbal IQ were considered. Poor readers were found to perform significantly worse than normal readers in all the examined EF skills. Correlation and regression results revealed a relatively different nature of the relationship between EF and reading in poor readers as compared with normal readers. Inhibition control predicted reading outcomes in poor readers only, while cognitive flexibility predicted reading outcomes in normal readers only. Working memory was significantly correlated to word reading in poor readers and to reading comprehension in normal readers. The results are discussed in terms of the special characteristics of the Chinese language.

Female Mice are More Resistant to the Mixed-Field (67% Neutron + 33% Gamma) Radiation-Induced Injury in Bone Marrow and Small Intestine than Male Mice due to Sustained Increases in G-CSF and the Bcl-2/Bax Ratio and Lower miR-34a and MAPK Activation.

In nuclear and radiological incidents, overexposure to ionizing radiation is life-threatening. It is evident that radiation depletes blood cells and increases circulating cytokine/chemokine concentrations as well as mortality. While microglia cells of female mice have been observed to be less damaged by radiation than in male mice, it is unclear whether sex affects physio-pathological responses in the bone marrow (BM) and gastrointestinal system (GI). We exposed B6D2F1 male and female mice to 0, 1.5, 3, or 6 Gy with mixed-field radiation containing 67% neutron and 33% gamma at a dose rate of 0.6 Gy/min. Blood and tissues were collected on days 1, 4, and 7 postirradiation. Radiation increased cytokines/chemokines in the femurs and ilea of female and male mice in a dose-dependent manner. Cytokines and chemokines reached a peak on day 4 and declined on day 7 with the exception of G-CSF which continued to increase on day 7 in female mice but not in male mice. MiR-34a (a Bcl-2 inhibitor), G-CSF (a miR-34a inhibitor), MAPK activation (pro-cell death), and citrulline (a biomarker of entroepithelial proliferation), active caspase-3 (a biomarker of apoptosis) and caspase-1 activated gasdermin D (a pyroptosis biomarker) were measured in the sternum, femur BM and ileum. Sternum histopathology analysis with H&E staining and femur BM cell counts as well as Flt-3L showed that BM cellularity was not as diminished in females, with males showing a 50% greater decline on day 7 postirradiation, mainly mediated by pyroptosis as indicated by increased gasdermin D in femur BM samples. Ileum injury, such as villus height and crypt depth, was also 43% and 30%, respectively, less damaged in females than in males. The severity of injury in both sexes was consistent with the citrulline and active caspase-3 measurements as well as active caspase-1 and gasdermin D measurements, suggesting apoptosis and pyroptosis occurred. On day 7, G-CSF in the ileum of female mice continued to be elevated by sevenfold, whereas G-CSF in the ileum of male mice returned to baseline. Furthermore, G-CSF is known to inhibit miR-34a expression, which in ileum on day 1 displayed a 3- to 4-fold increase in female mice after mixed-field (67% neutron + 33% gamma) irradiation, as compared to a 5- to 9-fold increase in male mice. Moreover, miR-34a blocked Bcl-2 expression. Mixed-field (60% neutron + 33% gamma) radiation induced more Bcl-2 in females than in males. On day 7, AKT activation was found in the ileums of females and males. However, MAPK activation including ERK, JNK, and p38 showed no changes in the ileum of females (by 0-fold; P > 0.05), whereas the MAPK activation was increased in the ileum of males (by 100-fold; P < 0.05). Taken together, the results suggest that organ injury from mixed-field (67% neutron + 33% gamma) radiation is less severe in females than in males, likely due to increased G-CSF, less MAPK activation, low miR-34a and increased Bcl-2/Bax ratio.

Quantitative multidimensional phenotypes improve genetic analysis of laterality traits.

Handedness is the most commonly investigated lateralised phenotype and is usually measured as a binary left/right category. Its links with psychiatric and neurodevelopmental disorders prompted studies aimed at understanding the underlying genetics, while other measures and side preferences have been less studied. We investigated the heritability of hand, as well as foot, and eye preference by assessing parental effects (n ≤ 5028 family trios) and SNP-based heritability (SNP-h2, n ≤ 5931 children) in the Avon Longitudinal Study of Parents and Children (ALSPAC). An independent twin cohort from Hong Kong (n = 358) was used to replicate results from structural equation modelling (SEM). Parental left-side preference increased the chance of an individual to be left-sided for the same trait, with stronger maternal than paternal effects for footedness. By regressing out the effects of sex, age, and ancestry, we transformed laterality categories into quantitative measures. The SNP-h2 for quantitative handedness and footedness was 0.21 and 0.23, respectively, which is higher than the SNP-h2 reported in larger genetic studies using binary handedness measures. The heritability of the quantitative measure of handedness increased (0.45) compared to a binary measure for writing hand (0.27) in the Hong Kong twins. Genomic and behavioural SEM identified a shared genetic factor contributing to handedness, footedness, and eyedness, but no independent effects on individual phenotypes. Our analysis demonstrates how quantitative multidimensional laterality phenotypes are better suited to capture the underlying genetics than binary traits.

Exploring the Genetic and Environmental Etiologies of Phonological Awareness, Morphological Awareness, and Vocabulary Among Chinese-English Bilingual Children: The Moderating Role of Second Language Instruction.

This study investigated the associations among bilingual phonological awareness, morphological awareness, and vocabulary by focusing on their genetic and environmental etiologies. It also explored the influence of family socio-economic status (SES) and language exposure amount on the genetic and environmental effects. A twin study was conducted with 349 pairs of Chinese-English bilingual twins (mean age = 7.37 years). Cross-language transfer was found in phonological and morphological awareness but not in vocabulary knowledge. A common genetic overlap was found among these bilingual abilities. We also found a common shared environmental effect that may account for the cross-language transfer in phonological awareness and the associations among English abilities. SES and language exposure were significant environmental influences on bilingual phonological awareness and English vocabulary. More teaching in Chinese was related to a stronger genetic effect on Chinese morphological awareness, whereas more teaching in English was related to a stronger environmental impact on English abilities.

Resting state EEG network modularity predicts literacy skills in L1 Chinese but not in L2 English.

EEG network modularity, as a proxy for cognitive plasticity, has been proposed to be a more reliable neural marker than power and coherence in predicting learning outcomes. The present study examined the associations between resting state EEG network modularity and both L1 Chinese and L2 English literacy skills among 90 Hong Kong first to fifth graders. The modularity indices of different frequency bands were highly correlated with one another. An exploratory factor analysis, performed to extract a general modularity index, explained 77.1% of the total variance. The modularity index was positively associated with Chinese word reading, Chinese phonological awareness, Chinese morphological awareness, and Chinese reading comprehension but was not significantly correlated with English word reading or English morphological awareness. Findings suggest that resting state EEG network modularity is likely to serve as a reasonable, reliable, and cost-effective neural marker of the development of first language but not second language literacy skills.

Clinical application of circulating tumor DNA in breast cancer.

BACKGROUND: The recent advancement in massively parallel sequencing technologies has empowered liquid biopsies, in particular circulating tumor DNA (ctDNA) analysis, to be the new paradigm in personalized cancer management. Plasma ctDNA detection overcomes the current limitations in tumor tissue procurement and serves as a convenient and non-invasive method to capture tumor heterogeneity and genetic evolution along patients' cancer journey. In breast cancer, the current clinical application of ctDNA includes real-time monitoring of tumor response, detection of drug-resistant clones, assessing dynamic variations in tumor mutational landscape, identifying actionable mutations, detecting minimal residual disease and screening of early tumor. PURPOSE: This review aims to summarize the current clinical evidence of ctDNA application in the management of breast cancer.

Reciprocal effects of morphological awareness, vocabulary knowledge, and word reading: A cross-lagged panel analysis in Chinese.

There are strong correspondences among syllable, morpheme, and orthographic representations in Chinese. For this reason, bidirectional relationships have been hypothesized among morphological awareness, vocabulary knowledge, and word reading from an early age. Our study examined the reciprocity of these skills among Hong Kong Chinese primary school children. Data were collected from 160 first graders at two time points and were analyzed using a cross-lagged panel design with the three skills modeled simultaneously. No reciprocal pathways were demonstrated in the model; instead, unidirectional relationships emerged. Morphological awareness facilitated later word reading, and word reading facilitated later vocabulary knowledge. Results are discussed in relation to a developmental account of learning to read in Chinese.

Electroencephalography decoding of Chinese characters in primary school children and its prediction for word reading performance and development.

Research on what neural mechanisms facilitate word reading development in non-alphabetic scripts is relatively rare. The present study was among the first to adopt a multivariate pattern classification analysis to decode electroencephalographic signals recorded for primary school children (N = 236) while performing a Chinese character decision task. Chinese is an ideal script for studying the relationship between neural discriminability (i.e., decodability) of the orthography and behavioral word reading skills since the mapping from orthography to phonology is relatively arbitrary in Chinese. This was also among the first empirical attempts to examine the extent to which decoding performance can predict current and subsequent word reading skills using a longitudinal design. Results showed that neural activation patterns of real characters can be distinguished from activation patterns for pseudo-characters, non-characters, and random stroke combinations in both younger and older children. Topography of the transformed classifier weights revealed two distinct cognitive sub-processes underlying single character recognition, but temporal generalization analysis suggested common neural mechanisms between the distinct cognitive sub-processes. Suggestive evidence from correlational and hierarchical regression analyses showed that decoding performance, assessed on average 2 months before the year 2 behavioral testing, predicted both year 1 word reading performance and the development of word reading fluency over the year. Results demonstrate that decoding performance, one indicator of how the neural system is functionally organized in processing characters and character-like stimuli, can serve as a useful neural marker in predicting current word reading skills and the capacity to learn to read.

Effect of Twinning on Chinese and English Vocabulary Knowledge.

Vocabulary knowledge was tested in a native (Cantonese-Chinese) and foreign (English) language in 150 twins and 150 singletons aged 6-11 years, matched on age, gender, grade level, nonverbal intelligence, parents' education, family income, and number of siblings and household members. The singletons clearly outperformed the twins on the native vocabulary, but this "twinning effect" was much less noticeable for the foreign vocabulary. The effect on English vocabulary was further reduced after exposure to English at home was controlled. Given that these participants learned most of their English in school rather than home, the present findings support the notion that the twinning effect is associated with increased competition for family interaction in twins compared with singletons.

Ghrelin, a novel therapy, corrects cytokine and NF-κB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma.

BACKGROUND: Compared to radiation injury alone (RI), radiation injury combined wound (CI) further enhances acute radiation syndrome and subsequently mortality. We previously reported that therapy with Ghrelin, the 28-amino-acid-peptide secreted from the stomach, significantly increased 30-day survival and mitigated hematopoietic death by enhancing and sustaining granulocyte-colony stimulating factor (G-CSF) and keratinocyte chemoattractant (KC) in the blood and bone marrow; increasing circulating white blood cell depletion; inhibiting splenocytopenia; and accelerating skin-wound healing on day 30 after CI. Herein, we aimed to study the efficacy of Ghrelin on intestinal injury at early time points after CI. METHODS: B6D2F1/J female mice were exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral), followed by 15% total-body-surface-area skin wounds. Several endpoints were measured: at 4-5 h and on days 1, 3, 7, and 15. RESULTS: Ghrelin therapy mitigated CI-induced increases in IL-1ß, IL-6, IL-17A, IL-18, KC, and TNF-α in serum but sustained G-CSF, KC and MIP-1α increases in ileum. Histological analysis of ileum on day 15 showed that Ghrelin treatment mitigated ileum injury by increasing villus height, crypt depth and counts, as well as decreasing villus width and mucosal injury score. Ghrelin therapy increased AKT activation and ERK activation; suppressed JNK activation and caspase-3 activation in ileum; and reduced NF-κB, iNOS, BAX and Bcl-2 in ileum. This therapy recovered the tight junction protein and mitigated bacterial translocation and lipopolysaccharides levels. The results suggest that the capacity of Ghrelin therapy to reduce CI-induced ileum injury is mediated by a balanced NF-κB-AKT-MAPK network that leads to homeostasis of pro-inflammatory and anti-inflammatory cytokines. CONCLUSIONS: Our novel results are the first to suggest that Ghrelin therapy effectively decreases intestinal injury after CI.

Prevalence and heritability of handedness in a Hong Kong Chinese twin and singleton sample.

BACKGROUND: Left-handedness prevalence has been consistently reported at around 10% with heritability estimates at around 25%. Higher left-handedness prevalence has been reported in males and in twins. Lower prevalence has been reported in Asia, but it remains unclear whether this is due to biological or cultural factors. Most studies are based on samples with European ethnicities and using the preferred hand for writing as key assessment. Here, we investigated handedness in a sample of Chinese school children in Hong Kong, including 426 singletons and 205 pairs of twins, using both the Edinburgh Handedness Inventory and Pegboard Task. RESULTS: Based on a binary definition of writing hand, we found a higher prevalence of left-handedness (8%) than what was previously reported in Asian datasets. We found no evidence of increased left-handedness in twins, but our results were in line with previous findings showing that males have a higher tendency to be left-handed than females. Heritability was similar for both hand preference (21%) and laterality indexes (22%). However, these two handedness measures present only a moderate correlation (.42) and appear to be underpinned by different genetic factors. CONCLUSION: In summary, we report new reference data for an ethnic group usually underrepresented in the literature. Our heritability analysis supports the idea that different measures will capture different components of handedness and, as a consequence, datasets assessed with heterogeneous criteria are not easily combined or compared.

Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Event-related potentials during Chinese single-character and two-character word reading in children.

Word reading involves a series of cognitive processes, from lower-level visual processing to word semantic retrieval. To investigate the timing of the underlying neurocognitive processes in reading, the current study examined the electrophysiological correlates of cognitive functions associated with traditional Chinese word reading in Hong Kong children (Age: M = 8.19, SD = 0.82 years old) using event-related potentials (ERPs). A single-character lexical decision task and a two-character word lexical decision task were used to explore different levels of Chinese word processing. One-hundred ten children's data were analyzed. Results revealed that radical level processing was related to a P1 component at as early as 130 ms. Character-level processing was related to an N1 component from 218 ms onwards. Two-character word semantic processing was related to an N400-like component at as early as 450 ms. The results show a similar time course of visual word processing as previously reported in alphabetic languages, consistent with increasing specialization in the ventral visual stream for increasing wordlikeness leading to processing of linguistic aspects in higher-level language regions.

Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: A propensity score matched analysis.

BACKGROUND: This study compared outcomes of nonresectable hepatocellular carcinoma (HCC) who had transarterial chemoembolization (TACE) vs. stereotactic body radiation therapy (SBRT) after TACE (TACE + SBRT). METHODS: This was a retrospective study of 2 centers in Hong Kong. There were 49 patients who had TACE + SBRT and 202 patients who had TACE alone. Propensity score matching was used to adjust for differences in patients' demographics and tumor characteristics between the 2 groups. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS) and treatment-related toxicity. RESULTS: After matching, 49 patients were in the TACE + SBRT group and 98 patients in the TACE group with similar baseline characteristics. The 1-&3-year OS were better in TACE + SBRT group (67.2 vs. 43.9% and 36.5 vs. 13.3%, p = 0.003). The 1-&3-year PFS was also better in TACE + SBRT group (32.5 vs. 21.4% and 15.1 vs. 5.1%, p = 0.012). Radiological disease control was better in the TACE + SBRT group (98 vs. 56.7%). Risk of severe toxicity was uncommon in both treatment arms. TACE + SBRT was an independent good prognostic factor for OS and PFS in multivariate analysis, whereas AFP>200 ng/ml, large tumor and multiple tumors predicted worse OS. CONCLUSION: TACE + SBRT is safe and results in better survivals in nonresectable HCC patients.

Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma.

PURPOSE: We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B-C hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child-Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6â€¯× 5-8 Gy or 5-10â€¯× 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated. RESULTS: The patients' characteristics were: median age 60 years (range 28-87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0-23.6 cm) and 751 cm3 (range 41-4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/ß = 10) was 37.3 Gy2 (range, 28-72 Gy2). The median follow-up time was 16.8 months (range, 3-96 months). The objective RR was 68% and the 1­year LC rate was 93.6% (95% CI, 87.6-100%). The median OS was 19.8 months (95% CI, 11.6-30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury. CONCLUSION: Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B-C HCC with appropriate patient selection. Further prospective trials are warranted.