Post-radiotherapy stage III/IV non-small cell lung cancer radiomics research: a systematic review and comparison of CLEAR and RQS frameworks.

BACKGROUND: Lung cancer, the second most common cancer, presents persistently dismal prognoses. Radiomics, a promising field, aims to provide novel imaging biomarkers to improve outcomes. However, clinical translation faces reproducibility challenges, despite efforts to address them with quality scoring tools. OBJECTIVE: This study had two objectives: 1) identify radiomics biomarkers in post-radiotherapy stage III/IV nonsmall cell lung cancer (NSCLC) patients, 2) evaluate research quality using the CLEAR (CheckList_for_EvaluAtion_of_Radiomics_research), RQS (Radiomics_Quality_Score) frameworks, and formulate an amalgamated CLEAR-RQS tool to enhance scientific rigor. MATERIALS AND METHODS: A systematic literature review (Jun-Aug 2023, MEDLINE/PubMed/SCOPUS) was conducted concerning stage III/IV NSCLC, radiotherapy, and radiomic features (RF). Extracted data included study design particulars, such as sample size, radiotherapy/CT technique, selected RFs, and endpoints. CLEAR and RQS were merged into a CLEAR-RQS checklist. Three readers appraised articles utilizing CLEAR, RQS, and CLEAR-RQS metrics. RESULTS: Out of 871 articles, 11 met the inclusion/exclusion criteria. The Median cohort size was 91 (range: 10-337) with 9 studies being single-center. No common RF were identified. The merged CLEAR-RQS checklist comprised 61 items. Most unreported items were within CLEAR's "methods" and "open-source," and within RQS's "phantom-calibration," "registry-enrolled prospective-trial-design," and "cost-effective-analysis" sections. No study scored above 50% on RQS. Median CLEAR scores were 55.74% (32.33/58 points), and for RQS, 17.59% (6.3/36 points). CLEAR-RQS article ranking fell between CLEAR and RQS and aligned with CLEAR. CONCLUSION: Radiomics research in post-radiotherapy stage III/IV NSCLC exhibits variability and frequently low-quality reporting. The formulated CLEAR-RQS checklist may facilitate education and holds promise for enhancing radiomics research quality. CLINICAL RELEVANCE STATEMENT: Current radiomics research in the field of stage III/IV postradiotherapy NSCLC is heterogenous, lacking reproducibility, with no identified imaging biomarker. Radiomics research quality assessment tools may enhance scientific rigor and thereby facilitate radiomics translation into clinical practice. KEY POINTS: There is heterogenous and low radiomics research quality in postradiotherapy stage III/IV nonsmall cell lung cancer. Barriers to reproducibility are small cohort size, nonvalidated studies, missing technical parameters, and lack of data, code, and model sharing. CLEAR (CheckList_for_EvaluAtion_of_Radiomics_research), RQS (Radiomics_Quality_Score), and the amalgamated CLEAR-RQS tool are useful frameworks for assessing radiomics research quality and may provide a valuable resource for educational purposes in the field of radiomics.

Current state of radiomic research in pancreatic cancer: focusing on study design and reproducibility of findings.

OBJECTIVES: To critically appraise methodology and reproducibility of published studies on CT radiomics of pancreatic ductal adenocarcinoma (PDAC). METHODS: PRISMA literature search of MEDLINE, PubMed, and Scopus databases was conducted from June to August 2022 relating to CT radiomics human research articles pertaining to PDAC diagnosis, treatment, and/ or prognosis, utilising Image Biomarker Standardisation Initiative-compliant (IBSI) radiomic software. Keyword search included [pancreas OR pancreatic] AND [radiomic OR [quantitative AND imaging] OR [texture AND analysis]]. Analysis included cohort size, CT protocol used, radiomic feature (RF) extraction, segmentation, and selection, software used, outcome correlation, and statistical methodology, with focus on reproducibility. RESULTS: Initial search yielded 1112 articles; however, only 12 articles met all inclusion/exclusion criteria. Cohort sizes ranged from 37 to 352 (median = 106, mean = 155.8). CT slice thickness varied among studies (4 using ≤ 1 mm, 5 using > 1 to 3 mm, 2 using > 3 to 5 mm, 1 not specifying). CT protocol varied (5 using a single portal-venous (pv)-phase, 5 using a pancreas protocol, 1 study using a non-contrast protocol). RF extraction and segmentation were heterogeneous (RF extraction: 5 using pv-phase, 2 using late arterial, 4 using multi-phase, 1 using non-contrast phase; RF selection: 3 pre-selected, 9 software-selected). 2D/3D RF segmentation was diverse (2D in 6, 3D in 4, 2D and 3D in 2 studies). Six different radiomics software were used. Research questions and cohort characteristics varied, ultimately leading to non-comparable outcome results. CONCLUSION: The current twelve published IBSI-compliant PDAC radiomic studies show high variability and often incomplete methodology resulting in low robustness and reproducibility. CLINICAL RELEVANCE STATEMENT: Radiomics research requires IBSI compliance, data harmonisation, and reproducible feature extraction methods for non-invasive imaging biomarker discoveries to be valid. This will ensure a successful clinical implementation and ultimately an improvement of patient outcomes as part of precision and personalised medicine. KEY POINTS: • Current state of radiomics research in pancreatic cancer shows low software compliance to the Image Biomarker Standardisation Initiative (IBSI). • IBSI-compliant radiomics studies in pancreatic cancer are heterogeneous and not comparable, and the majority of study designs showed low reproducibility. • Improved methodology and standardisation of practice in the emerging field of radiomics has the potential of this non-invasive imaging biomarker in the management of pancreatic cancer.

Real-world staging computed tomography scanning technique and important reporting discrepancies in pancreatic ductal adenocarcinoma.

BACKGROUND: Computed tomography (CT) is the first-line staging imaging modality for pancreatic ductal adenocarcinoma (PDAC) which determines resectability and treatment pathways. METHODS: Between January 2016 and December 2019, prospectively collated data from two Australian cancer centres was extracted from the PURPLE Pancreatic Cancer registry. Real-world staging CTs and corresponding reports were blindly reviewed by a sub-specialist radiologist and compared to initial reports. RESULTS: Of 131 patients assessed, 117 (89.3%) presented with symptoms, 74 (56.5%) CTs included slices ≤3 mm thickness and CT pancreas protocol was applied in 69 (52.7%) patients. Initial reports lacked synoptic reporting in 131 (100%), tumour identification in 2 (1.6%) and tumour measurement in 13 (9.9%) cases. Tumour-vascular relationship reporting was missing in 69-109 (52.7-83.2%) for regarding the key arterial and venous structures that is required to assess resectability. Initial reports had no comment on venous thrombus or venous collaterals in 80 (61.1%) and 109 (83.2%) and lacked locoregional lymphadenopathy interpretation in 13 (9.9%) cases. Complete initial staging report was present in 72 (55.0%) patients. Sub-specialist radiological review resulted in down-staging in 16 (22.2%) and up-staging in 1 (1.4%) patient. Staging discrepancies were mainly regarding metastatic disease (12, 70.6%) and tumour-vascular relationship (5, 29.4%). CONCLUSION: Real-world staging imaging in PDAC patients show low proportion of dedicated CT pancreas protocol, high proportion of incomplete staging reports and no synoptic reporting. The most common discrepancy between initial and sub-specialist reporting was regarding metastases and tumour-vascular relationship assessment resulting in sub-specialist down-staging in almost every fifth case.

Enzyme-Treated Zizania latifolia Ethanol Extract Protects from UVA Irradiation-Induced Wrinkle Formation via Inhibition of Lysosome Exocytosis and Reactive Oxygen Species Generation.

Ultraviolet A (UVA) is a risk factor for photoaging and wrinkle formation. Zizania latifolia is an herbaceous perennial plant. It contains many bioactive compounds such as tricin that show antioxidative and anti-inflammatory effects. The aim of this study was to investigate the antiwrinkle effect of a mixture of hydrolytic enzyme (cellulase, hemicellulase and pectinase)-treated Z. latifolia extract (ZLE) and tricin on UVA-irradiated human dermal fibroblasts (HDFs) and SKH-1 hairless mice. Treatment of UVA-irradiated HDF cells with ZLE and tricin significantly decreased UVA induced-plasma membrane rupture, generation of ROS, expression levels of total and secreted lysosomal associated membrane protein (LAMP-1), cathepsin B and metalloproteinases (MMPs) and inhibited NF-κB activation. In the animal study, UVA-damaged epidermal and dermal tissues were repaired by the ZLE and tricin treatments. Administration of ZLE or tricin to UVA-irradiated animals recovered skin surface moisture and collagen fiber in dermal tissue. Treatment of ZLE or tricin decreased wrinkle formation, secretion of MMPs and expression levels of vascular endothelial growth factor (VEGF) and cathepsin B, and increased the expression level of collagen-1 in UVA-irradiated animals. Overall, the ZLE and tricin treatments decreased the skin damage induced by UVA irradiation via inhibition of lysosomal exocytosis and ROS generation. Therefore, ZLE and tricin are promising as antiwrinkle and antiphotoaging agents.

Gamma Aminobutyric Acid Increases Absorption of Glycine-Bound Iron in Mice with Iron Deficiency Anemia.

Iron deficiency is a leading cause of anemia. Amino acids are known to promote the absorption of both soluble and insoluble iron. The bioavailability of organic iron is higher than that of inorganic iron. Therefore, the aim of this study was to evaluate the iron absorption of glycine-bound iron (an organic iron) and a combination of glycine-bound iron and gamma aminobutyric acid (GABA) in mice with iron deficiency anemia (IDA). Mice were fed an iron-deficient diet for 3 weeks, followed by oral administration of GABA, inorganic iron, glycine-bound iron, or GABA plus glycine-bound iron for 5 weeks. Ferritin storage in the spleen was measure by immunohistochemistry (IHC). Iron deposition in the liver and spleen tissues was analyzed using atomic absorption spectrometry. Expression levels of iron absorption-related genes were measured by quantitative real-time polymerase chain reaction (qPCR). Iron absorption was enhanced in the glycine-bound iron-treated group compared with the inorganic iron-treated group. Hemoglobin, serum Fe, ferritin, and liver iron levels did not increase in mice treated with GABA alone. However, mice administered GABA in combination with glycine-bound iron showed higher iron absorption than those administered organic iron alone. Our results indicate that glycine-bound iron in combination with GABA might exert a synergistic effect on iron absorption and bioavailability, suggesting that the addition of GABA to existing iron supplements might increase their effectiveness for treating IDA.

VSX1 gene and keratoconus: genetic analysis in Korean patients.

PURPOSE: The visual system homeobox 1 (VSX1) gene variants have recently been shown to be associated with keratoconus. To replicate this finding, we performed a genetic analysis of the VSX1 gene in a Korean case-control sample. METHODS: Patients with keratoconus and healthy control subjects were recruited from Seoul National University Hospital. A diagnosis of keratoconus was made based on clinical examinations and the presence of characteristic topographic features. For all patients and controls, the whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing. RESULTS: Fifty-three patients with keratoconus and 100 healthy volunteers were included. We observed 2 novel missense substitutions (Leu17Val and Val199Leu) and 1 previously reported substitution (Gly160Val) in 6 of the 53 affected probands. Because these substitutions have been identified in unaffected individuals, they were not considered to be pathogenic. No intragenic polymorphism was associated with a significantly increased risk of keratoconus. CONCLUSIONS: We cannot confirm the previously reported association of the VSX1 gene variants with keratoconus. Our results suggest that the VSX1 gene and its mutations with amino acid changes do not play a major role in the pathogenesis of keratoconus.

Molecular genetic characteristics of X-linked retinoschisis in Koreans.

PURPOSE: X-linked retinoschisis (XLRS) is a recessively inherited disorder that causes macular degeneration and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the RS1 gene in Korean patients with XLRS, and aimed to provide genetic information of XLRS in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of RS1 were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had RS1 mutations. In one patient, neither sequence variation nor deletion or duplication in RS1 was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had XLRS. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean XLRS will be helpful for understanding the worldwide spectrum of RS1 mutation.

Investigation of the association between normal-tension glaucoma and single nucleotide polymorphisms in natriuretic peptide gene.

PURPOSE: The expression of natriuretic peptides in the neural bundles of the anterior portion of the optic nerves and their functions in regulating vessel tone and blood flow may suggest a possible role in the pathogenesis of glaucoma. The purpose of this study was to investigate the association between normal-tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa) and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A, and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene were determined using the restriction fragment length polymorphism and the SNaPshot methods. The genotype and allele frequencies of these polymorphisms in patients with NTG and normal controls were compared using the Fisher's exact test and the chi-square test. RESULTS: In both groups, the genotype distributions were in accordance with the Hardy-Weinberg equilibrium. There was no significant difference in the frequency of the Nppa and Npr1 alleles or genotypes in the normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease.

Current radiological management of intussusception in children.

Intussusception is the most common abdominal emergency situation in infants and small children. There has been great progress in diagnostic and therapeutic management of intussusception. Ultrasound (US) has been shown to be the first-choice imaging technique in diagnosing intussusception for reasons of high accuracy, simultaneous exclusion of differential diagnoses, and disclosure of additional pathologies. Controversial opinions exist worldwide concerning the nonoperative treatment of intussusception in infants and children. Pneumatic reduction under fluoroscopic guidance and hydrostatic reduction under US monitoring are the preferred techniques. The aim should be a success rate of at least 90% in idiopathic intussusception. This review summarizes different types of intussusception and outlines diagnostic aspects as well as several treatment concepts.

Investigation of the association between OPA1 polymorphisms and normal-tension glaucoma in Korea.

PURPOSE: OPA1, the gene responsible for autosomal dominant optic atrophy, represents a good candidate gene for normal-tension glaucoma (NTG). Single nucleotide polymorphisms on intervening sequence (IVS) 8 of the OPA1 gene (IVS8+4C>T; +32T>C) were recently found to be strongly associated with NTG in a Caucasian population. We investigated whether these polymorphisms in the OPA1 gene were associated with NTG in Korea. PATIENTS AND METHODS: Sixty-five Korean NTG patients and 101 healthy Korean subjects were enrolled. DNA from peripheral blood leukocytes was extracted and the genotypes of two polymorphisms (IVS8+4C>T; +32T>C) in the OPA1 gene were determined using the restriction fragment length polymorphism method. The genotype and allele frequencies of two polymorphism in patients with NTG and normal controls were compared using the Fisher exact test and the chi test. Frequencies of haplotypes and haplotypes groups were also analyzed to assess the combined effect of two polymorphisms. RESULTS: The frequencies of the CT genotype of IVS8+4C>T, CC genotype of IVS8+32T>C, and TT genotype of IVS8+32T>C were not significantly different between NTG patients and controls (4.6% versus 0.0%, P = 0.058 by the Fisher exact test; 10.8% versus 4.0%, P = 0.11 by the Fisher exact test; 61.5% versus 67.3%, P = 0.45 by the chi test, respectively). Any haplotype or haplotype group of IVS8+4C>T and IVS8+32T>C was not associated with NTG, and the C allele of IVS8+32T>C was not a significant modifier of IVS8+4C>T. CONCLUSIONS: There were no significant associations between IVS8+4C>T; +32T>C polymorphisms and NTG in the Korean population. These results do not support the results in Caucasians and indicate that ethnic differences may exist in the association between polymorphisms in the OPA1 gene and NTG.