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.
This study compared outcomes of nonresectable hepatocellular carcinoma (HCC) who had transarterial chemoembolization (TACE) vs. stereotactic body radiation therapy (SBRT) after TACE (TACE + SBRT).
...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.
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.
TACE + SBRT is safe and results in better survivals in nonresectable HCC patients.
This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery.
This study included 31 consecutive patients with ...unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival.
Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer).
Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.
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 6 × 5–8 Gy or 5–10 × 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 cm
3
(range 41–4009 cm
3
), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/β = 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 1‑year 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.
Objectives: Pulmonary dysfunction following lung ischaemia–reperfusion is a well-known phenomenon, which may contribute to post-cardiac surgical morbidity. The process is associated with pulmonary ...inflammatory response and cellular apoptosis. Early molecular mechanisms leading to such lung injury remain largely unknown. We examined whether lung ischaemia and reperfusion cause significant expression changes in numerous genes in the lungs involved in pulmonary apoptosis and other cellular processes by using oligonucleotide microarrays in an experimental model of rodent lung ischaemia–reperfusion injury. Methods: Sprague-Dawley rodents (n = 5 in each group) were anaesthetised and underwent controlled ventilation, with varying durations of warm lung ischaemia (60 and 90 min) followed by a short reperfusion period. The right middle lobe of the lung was harvested. Gene expression changes in the lungs were analysed by rodent DNA microarray chips, and reverse transcription polymerase chain reaction (RT-PCR) performed to validate changes in gene expression. Results: Significant expression changes, with reference to false discovery rate (FDR) controls, were detected in over 80 genes following controlled lung ventilation, and more than 50 were up-regulated more than 2-fold. Lung ischaemia–reperfusion caused expression changes in over 50 additional genes, including many novel genes not previously associated with lung ischaemia–reperfusion. Up-regulated genes identified include those associated with apoptosis, inflammation and cell-cycle control. Conclusions: Large numbers of genes relating to cell metabolism, transcription control, inflammation and apoptosis were significantly up- and down-regulated following controlled ventilation and early lung ischaemia–reperfusion, consistent with previous studies. In addition, novel genes related to lung injury were identified. These genetic signatures provide new insights into early molecular mechanisms of ischaemia–reperfusion lung injury and help refine therapeutic strategies to lessen pulmonary dysfunction following cardiac surgery.
Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 (FLT3) gene occurs in 30% of acute myeloid leukemias (AMLs) and confers a poor prognosis. Thirteen relapsed or chemo-refractory ...FLT3-ITD+ AML patients were treated with sorafenib (200-400 mg twice daily). Twelve patients showed clearance or near clearance of bone marrow myeloblasts after 27 (range 21-84) days with evidence of differentiation of leukemia cells. The sorafenib response was lost in most patients after 72 (range 54-287) days but the FLT3 and downstream effectors remained suppressed. Gene expression profiling showed that leukemia cells that have become sorafenib resistant expressed several genes including ALDH1A1, JAK3, and MMP15, whose functions were unknown in AML. Nonobese diabetic/severe combined immunodeficiency mice transplanted with leukemia cells from patients before and during sorafenib resistance recapitulated the clinical results. Both ITD and tyrosine kinase domain mutations at D835 were identified in leukemia initiating cells (LICs) from samples before sorafenib treatment. LICs bearing the D835 mutant have expanded during sorafenib treatment and dominated during the subsequent clinical resistance. These results suggest that sorafenib have selected more aggressive sorafenib-resistant subclones carrying both FLT3-ITD and D835 mutations, and might provide important leads to further improvement of treatment outcome with FLT3 inhibitors.
This work evaluated the prognostic performance of Child-Pugh (CP), albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) scores in hepatocellular carcinoma (HCC) patients undergoing ...radiotherapy (RT).
The study included 174 consecutive patients with 63% at CP A5 (
= 110) and 34% at CP A6 (
= 64). The median ALBI score was -2.39 (range: -3.61 to -1.41) with 34.5% at grade A1 (
= 60) and 65.5% at grade A2 (
= 114). The median PALBI score was -2.39 (range -3.39 to -1.24) with 33.3% at grade 1 (
= 58), 41.4% at grade 2 (
= 72) and 25.3% at grade 3 (
= 44). With a median follow-up of 21.7 months, the median OS of the entire cohort was 22.2 months. OS was significantly associated with the PALBI grade (
= 0.002) and for the ALBI grade (
= 0.00495), but not for the CP score (
= 0.46). The PALBI grade has a significantly higher AUC compared than the ALBI grade or CP scores in predicting OS. The PALBI grade was predictive of CP score decline ≥2 (20% grade 3 vs. 5.3% grade 1/2
= 0.05) but the ALBI and CP scores were not.
Among CP A HCC patients receiving radiotherapy, the PALBI and ALBI grade maybe a better prognostic tool than the CP score. The role of PALBI in predicting liver toxicity warranted further exploration.
We retrospectively reviewed HCC patients treated with individualized hypo-fractionated radiotherapy (IHRT) using stereotactic technique from 2006 to 2015. We collected CP, ALBI and PALBI scores prior to treatment and analyzed their correlation with overall survival (OS) and liver toxicity.
We demonstrate that functional polyelectrolyte multilayer (PEM) patches can be attached to a fraction of the surface area of living, individual lymphocytes. Surface-modified cells remain viable at ...least 48 h following attachment of the functional patch, and patches carrying magnetic nanoparticles allow the cells to be spatially manipulated using a magnetic field. The patch does not completely occlude the cellular surface from the surrounding environment; this approach allows a functional payload to be attached to a cell that is still free to perform its native functions, as suggested by preliminary studies on patch-modified T-cell migration. This approach has potential for broad applications in bioimaging, cellular functionalization, immune system and tissue engineering, and cell-based therapeutics where cell-environment interactions are critical.
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.
Neural activation patterns of Chinese characters can be decoded and significantly distinguished from those of pseudo‐characters, non‐characters, and stroke combinations in children. Decoding performance tended to be associated with word reading development assessed using a longitudinal design and may be a useful neural marker to predict reading development.
The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk ...factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).
The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy.
Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.
The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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