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Evaluation of blood vessel network formation and visual field defect in optic disc melanocytoma
Full text linkAim: To investigate the association between visual field defects and blood vessel network (BVN) formation in optic disc melanocytomas (ODMs) using optical coherence tomography angiography (OCTA).
Methods: Single-centre, retrospective case series of 32 eyes of 32 patients with ODM, in which eyes were divided into two groups based on complete and incomplete BVN formations.
Results: OCTA revealed incomplete BVN formation in 16 of 32 ODMs. The location of BVN absence corresponded to the location of hypofluorescence from fluorescein angiography (FA) in 12 (75%) and to the location of visual field defect in 13 (81%) ODMs in the incomplete BVN group. Perimetric indices were significantly worse in the incomplete BVN group than in the complete BVN group. Linear regression of mean deviation (MD) and Visual Field Index (VFI) on the area of BVN absence were statistically significant (p=0.01 and p=0.003, respectively), whereas linear regressions of MD and VFI on the tumour area were not statistically significant (both p=0.09) in the incomplete BVN group.
Conclusion: The location of BVN absence within ODMs corresponded to the location of visual field defect and the location of FA hypofluorescence. Visual field defect was more severe in the incomplete BVN group than in the complete BVN group. Visual field defect was more significantly associated with the area of BVN absence than the tumour area.ope
Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors
Full text linkBACKGROUND: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β trap) fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy.
MATERIALS AND METHODS: In this expansion cohort of NCT02517398-a global, open-label, phase I trial-adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee); secondary endpoints included safety.
RESULTS: Eighty-three eligible patients (62 [74.7%] treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8%; 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 [3.6%]) and fatigue, eczema, and pruritus (2 each [2.4%]). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa.
CONCLUSION: Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy. © The Author(s) 2022. Published by Oxford University Press.ope
Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
Full text linkOsimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to first-line osimertinib. Next-generation sequencing assesses circulating-tumor DNA from paired plasma samples (baseline and disease progression/treatment discontinuation) in patients with baseline EGFRm. No EGFR T790M-mediated acquired resistance are observed; most frequent resistance mechanisms are MET amplification (n = 17; 16%) and EGFR C797S mutations (n = 7; 6%). Future research investigating non-genetic acquired resistance mechanisms is warranted. © 2023. The Author(s).ope
Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14)
No full textBackground: HER2 overexpression or amplification, which is present in 15% of all cases of biliary tract cancer, has been identified as a druggable molecular target by genomic profiling. In the phase 3 ABC-06 trial, the folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen showed a survival benefit compared with active symptom control as second-line therapy for biliary tract cancer. We aimed to evaluate the clinical activity of FOLFOX plus anti-HER2 antibody trastuzumab as a second-line or third-line treatment for HER2-positive biliary tract cancer.
Methods: This study was an investigator-initiated, open-label, non-randomised, single-arm, multi institutional, phase 2 trial in participants aged 19 years or older with HER2-positive (defined as immunohistochemistry 3+ or immunohistochemistry 2+ and in-situ hybridisation positive or ERBB2 gene copy number ≥6·0 by next-generation sequencing) biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) who progressed on chemotherapy containing gemcitabine and cisplatin (with one or two previous chemotherapy lines permitted). In cycle one, patients received intravenous trastuzumab-pkrb at 6 mg/kg on day 1, and FOLFOX (consisting of intravenous oxaliplatin [85 mg/m2], intravenous leucovorin [200 mg/m2], and fluorouracil [400 mg/m2 bolus] all on day 1, and fluorouracil [2400 mg/m2 infusion] on days 1-2. In cycle two onwards, participants were administered intravenous trastuzumab-pkrb at 4 mg/kg and FOLFOX, every 2 weeks, until unacceptable toxic effects or disease progression. The primary endpoint of the study was objective response rate based on RECIST version 1.1, assessed in the participants who completed at least one study cycle. The response rate threshold for a positive objective response rate was 25%. This trial is registered with ClinicalTrials.gov (NCT04722133) and is ongoing.
Findings: 34 participants were enrolled between June 26, 2020, and Sept 1, 2021. At the time of data cutoff on May 1, 2022, median follow-up was 13·0 months (IQR 11·0-16·9), with three participants remaining on treatment. Ten patients had a partial response and 17 had stable disease; the overall response rate was 29·4% (95% CI 16·7-46·3) and the disease control rate was 79·4% (95% CI 62·9-89·9). Median progression-free survival was 5·1 months (95% CI 3·6-6·7); median overall survival was 10·7 (95%CI 7·9-not reached). The most common treatment-related grade 3 or 4 adverse events were neutropenia (ten [29%] participants with grade 3 and nine [26%] with grade 4), grade 3 anaemia (five [15%] participants), and grade 3 peripheral sensory neuropathy (four [12%] participants). There were no treatment-related cardiac toxic effects or deaths. The overall health assessment (EuroQoL-VAS) score did not change significantly throughout the treatment. Sensory and motor neuropathy symptoms as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy twenty-item scale questionnaire did not change significantly over time.
Interpretation: For HER2-positive biliary tract cancer, second-line or third-line trastuzumab biosimilar plus FOLFOX exhibited promising activity with acceptable toxicity, warranting further investigation.
Funding: Boryung Pharmaceutical, Celltrion, National Research Foundation of Korea, National R&D Program for Cancer Control through the National Cancer Center, Yonsei University College of Medicine.
Copyright © 2022 Elsevier Ltd. All rights reserved.restrictio
Pre- and Immediate Post-Kasai Portoenterostomy Shear Wave Elastography for Predicting Hepatic Fibrosis and Native Liver Outcomes in Patients With Biliary Atresia
Full text linkObjective: To evaluate the feasibility of ultrasound shear wave elastography (SWE) for predicting hepatic fibrosis and native liver outcomes in patients with biliary atresia.
Materials and Methods: This prospective study included 33 consecutive patients with biliary atresia (median age, 8 weeks [interquartile range, 6–10 weeks]; male:female ratio, 15:18) from Severance Children’s Hospital between May 2019 and February 2022. Preoperative (within 1 week from surgery) and immediate postoperative (on postoperative days [PODs] 3, 5, and 7) ultrasonographic findings were obtained and analyzed, including the SWE of the liver and spleen. Hepatic fibrosis, according to the METAVIR score at the time of Kasai portoenterostomy and native liver outcomes during postsurgical follow-up, were compared and correlated with imaging and laboratory findings. Poor outcomes were defined as intractable cholangitis or liver transplantation. The diagnostic performance of SWE in predicting METAVIR F3–F4 and poor hepatic outcomes was analyzed using receiver operating characteristic (ROC) analyses.
Results: All patients were analyzed without exclusion. Perioperative advanced hepatic fibrosis (F3–F4) was associated with older age and higher preoperative direct bilirubin and SWE values in the liver and spleen. Preoperative liver SWE showed a ROC area of 0.806 and 63.6% (7/11) sensitivity and 86.4% (19/22) specificity at a cutoff of 17.5 kPa for diagnosing F3–F4. The poor outcome group included five patients with intractable cholangitis and three undergoing liver transplantation who showed high postoperative liver SWE values. Liver SWE on PODs 3–7 showed ROC areas of 0.783–0.891 for predicting poor outcomes, and a cutoff value of 10.3 kPa for SWE on POD 3 had 100% (8/8) sensitivity and 73.9% (17/23) specificity.
Conclusion: Preoperative liver SWE can predict advanced hepatic fibrosis, and immediate postoperative liver SWE can predict poor native liver outcomes in patients with biliary atresia.ope
Parotid gland evaluation of menopausal women with xerostomia using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method of MRI: a pilot study
No full textOBJECTIVES: This study aimed to analyze the quantitative fat fraction (FF) of the parotid gland in menopausal females with xerostomia using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method.
METHODS: A total 138 parotid glands of 69 menopausal females were enrolled in our study and participants were divided into normal group and xerostomia group. The xerostomia group was divided into those with or without Sjögren's syndrome. Participants underwent IDEAL-IQ sequences of MRI and the stimulated salivary flow test (s-SFR). The unpaired t-test was used to compare the FFs between the normal and xerostomia groups and between the subgroups with and without Sjögren's syndrome. The correlation between FF and s-SFR was analyzed by Pearson's correlation.
RESULTS: Excellent intra- and interobserver agreement during the measurement of FFs by IDEAL-IQ method (ICC>0.99, respectively). FF value in the xerostomia group was statistically significantly higher than the value in the normal group (p 0.05). Within the xerostomia group, FF value correlated negatively with s-SFR (p < 0.08).
CONCLUSIONS: The FF of the parotid gland was higher in the xerostomia group than in the normal group and FF value and s-SFR showed a negative correlation. Analyses of the FF using IDEAL-IQ in menopausal females can be helpful for the quantitative diagnosis of xerostomia.restrictio
Artificial intelligence assistance for women who had spot compression view: reducing recall rates for digital mammography
No full textBackground: Mammography yields inevitable recall for indeterminate findings that need to be confirmed with additional views.
Purpose: To explore whether the artificial intelligence (AI) algorithm for mammography can reduce false-positive recall in patients who undergo the spot compression view.
Material and Methods: From January to December 2017, 236 breasts from 225 women who underwent the spot compression view due to focal asymmetry, mass, or architectural distortion on standard digital mammography were included.
Three readers who were blinded to the study purpose, patient information, previous mammograms, following spot compression views, and any clinical or pathologic reports retrospectively reviewed 236 standard mammograms and determined the necessity of patient recall and the probability of malignancy per breast, first without and then with AI assistance. The performances of AI and the readers were evaluated with the recall rate, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.
Results: Among 236 examinations, 8 (3.4%) were cancers and 228 (96.6%) were benign. The recall rates of all three readers significantly decreased with AI assistance (P < 0.05). The reader-averaged recall rates significantly decreased with AI assistance regardless of breast composition (fatty breasts: 32.7% to 24.1%m P =0.002; dense breasts: 33.6% to 21.2%, P < 0.001). The reader-averaged AUC increased with AI assistance and was comparable to that of standalone AI (0.835 vs. 0.895; P =0.234). The reader-averaged specificity (71.2% to 79.8%, P < 0.001) and accuracy (71.3% to 79.7%, P<0.001) significantly improved with AI assistance.
Conclusion: AI assistance significantly reduced false-positive recall without compromising cancer detection in women with focal asymmetry, mass, or architectural distortion on standard digital mammography regardless of mammographic breast density.restrictio
Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans
Full text linkThis study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull's eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype-phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull's eye maculopathy. This trend was similar to previous genotype-phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.ope
Primary Localized Cutaneous Nodular Amyloidosis on Scalp Successfully Treated with Excision
Full text linkPrimary localized cutaneous nodular amyloidosis (PLCNA) is the rarest form of cutaneous amyloidosis, characterized by nodular deposits of light chain amyloids in the dermis and subcutaneous tissue, without apparent systemic involvement. One or several nodules are preferably located on the extremities, trunk, or face. The most useful stain for detecting amyloid fibrils is Congo red, which, when combined with polarized light, makes amyloid proteins appear apple-green under a microscope. Immunohistochemical staining can help identify the exact type of amyloid proteins. Although the exact etiology of PLCNA is unclear, removal of nodules by shaving or surgical excision has shown good results. To the best of our knowledge, only seven cases of PLCNA have yet been reported in the Korean literature. In three of these cases, the patients had lesions on the scalp. Herein, we present a case of a 34-year-old male with PLCNA on the scalp with all the results of immunohistochemical evaluation.ope
Various Applications of Purse-String Suture and Its Cosmetic Outcome in Cutaneous Surgical Defects
Full text linkBackground: Purse-string suture is a simple technique to reduce wound size and to achieve complete or partial closure of skin defects.
Objective: To classify situations in which purse-string sutures can be utilized and to assess the long-term size reduction and cosmetic outcome of the final scar.
Methods: Patients (93 from Severance hospital and 12 from Gangnam Severance hospital) in whom purse-string sutures were used between January 2015 and December 2019 were retrospectively reviewed. Wound site, final reconstruction method, repair duration, final wound size, and Vancouver scar scale were assessed.
Results: A total of 105 patients were reviewed. Lesions were located on the trunk (48 [45.7%]), limbs (32 [30.5%]), and face (25 [23.8%]). Mean ratio of wound length/primary defect length was 0.79±0.30. Multilayered purse-string suture showed the shortest duration from excision to final repair (p<0.001) and most effectively minimized the scar size (scar to defect size ratio 0.67±0.23, p=0.002). The average Vancouver scar scale measured at the latest followup visit at least 6 months postoperatively was 1.62, and the risk of hypertrophic scarring was 8.6%. There was no significant difference in the Vancouver scar scale and the risk of hypertrophic scarring between the different surgical method groups.
Conclusion: Purse-string sutures can be utilized in many stages of reconstruction to effectively reduce scar size without compromising the final cosmetic outcome. Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.ope