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Contact Dermatitis Apr 2024
Topics: Humans; Dermatitis, Allergic Contact; Epoxy Resins; Paresthesia; Dermatitis, Occupational; Nail Diseases; Patch Tests
PubMed: 38254251
DOI: 10.1111/cod.14506 -
Aging Jan 2024In real-world practice, most patients with lung cancer are diagnosed when they are aged ≥65 years. However, clinical trials tend to lack data for the elderly...
Effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with epidermal growth factor receptor-mutated advanced non-small-cell lung cancer: a multi-institute retrospective study.
BACKGROUND
In real-world practice, most patients with lung cancer are diagnosed when they are aged ≥65 years. However, clinical trials tend to lack data for the elderly population. Therefore, we aimed to describe the effectiveness and safety of afatinib, gefitinib, and erlotinib for elderly patients with epidermal growth factor receptor ()-mutated advanced non-small-cell lung cancer (NSCLC).
METHODS
Treatment-naïve patients with -mutated advanced NSCLC were enrolled at many hospitals in Taiwan. Patient characteristics and the effectiveness and safety of afatinib, gefitinib, and erlotinib were compared.
RESULTS
This study enrolled 1,343 treatment-naïve patients with -mutated advanced NSCLC, of whom 554 were aged <65 years, 383 were aged 65-74 years, 323 were aged 75-84 years, and 83 were aged ≥85 years. For elderly patients, afatinib was more effective, with a median progression-free survival (PFS) of 14.7 months and overall survival (OS) of 22.2 months, than gefitinib (9.9 months and 17.7 months, respectively) and erlotinib (10.8 months and 18.5 months, respectively; PFS: = 0.003; OS: = 0.026). However, grade ≥3 adverse events, including skin toxicities, paronychia, mucositis, and diarrhea, were more frequently experienced by patients receiving afatinib than those receiving gefitinib or erlotinib.
CONCLUSIONS
This large retrospective study provides real-world evidence of the effectiveness and safety of EGFR-TKIs for elderly patients with EGFR-mutated advanced NSCLC, a population that is often underrepresented in clinical trials and real-world evidence. Afatinib was more effective as a first-line treatment than gefitinib or erlotinib for elderly patients with -mutated advanced NSCLC.
Topics: Aged; Humans; Afatinib; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 38194721
DOI: 10.18632/aging.205395 -
Foot and Ankle Surgery : Official... Apr 2024Paronychia is a prevalent clinical disease affecting the soft tissue surrounding the nails. Most cases of toenail paronychia are commonly associated with ingrown... (Review)
Review
BACKGROUND
Paronychia is a prevalent clinical disease affecting the soft tissue surrounding the nails. Most cases of toenail paronychia are commonly associated with ingrown toenails. While conservative treatment is effective for mild cases of ingrown toenails, surgical intervention becomes necessary for moderate to severe cases, particularly when granulomas form.
OBJECTIVE
To provide a systematic understanding of these classic and modified procedures for surgeons to select the appropriate surgical interventions for patients suffering from moderate to severe ingrown toenails and discuss this technology's advantages and limitations for dermatologic surgery.
METHODS
A literature search was performed using PubMed/MEDLINE and Google Scholar databases. Studies discussing surgical intervention for ingrown toenails were included. Moreover, the surgical steps were meticulously depicted by detailed schematic diagrams.
RESULTS
These surgical techniques can be divided into three categories: matrix resection, debulking of periungual soft tissues, and the rotational flap technique. Each approach possesses distinct advantages and limitations.
CONCLUSION
For moderate to severe cases, surgical interventions may exhibit superior outcomes, faster recovery times, and lower recurrence rates. The surgeon must possess a comprehensive understanding and proficient skillset in various surgical techniques for ingrown toenails.
Topics: Humans; Nails; Paronychia; Nails, Ingrown; Surgical Flaps; Conservative Treatment
PubMed: 38177051
DOI: 10.1016/j.fas.2023.12.003 -
Pediatric Dermatology 2024Retronychia is characterized by proximal ingrowing of the nail plate into the proximal nail fold. It is always associated with the presence of two or more overlapping... (Observational Study)
Observational Study
BACKGROUND
Retronychia is characterized by proximal ingrowing of the nail plate into the proximal nail fold. It is always associated with the presence of two or more overlapping nail plates under the proximal nail fold, clinical signs of chronic proximal paronychia refractory to antimicrobial treatment, and a yellowish nail that does not grow. It mainly affects young female adults, with less than 30 pediatric cases described in the literature so far.
METHODS
Retrospective and observational study of patients between 0 and 18 years with a clinical and/or ultrasound diagnosis of retronychia attending a pediatric dermatology service between December 2020 and January 2022.
RESULTS
We identified 9 patients with retronychia, 7 girls and 2 boys. In all cases, the hallux nails were affected with 5 unilateral and 4 bilateral cases. On physical examination we observed the following signs: thickened and opaque nail plate (one patient), yellowish nail plate (7 patients), double nail plate (6 patients), and erythema with edema, pain, and suppuration of the proximal nail fold (7 patients). Ultrasound was performed in 7 patients and specific findings of retronychia were found in 5 of them. All patients received topical treatment and were referred for the appropriate surgical treatment. To date, only one patient underwent nail avulsion, which was followed by complete recovery.
CONCLUSIONS
Retronychia is underdiagnosed, particularly in the pediatric population. We present a series of 9 cases of retronychia in children, with clinical and ultrasonographic findings consistent with those of adults. We emphasize the importance of recognizing this entity, which will allow early and adequate treatment.
Topics: Humans; Male; Female; Child; Retrospective Studies; Nails, Ingrown; Adolescent; Child, Preschool; Infant; Paronychia; Ultrasonography; Nails
PubMed: 38128581
DOI: 10.1111/pde.15503 -
Cancers Nov 2023This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and...
Real-World Treatment Outcomes and Safety of Afatinib in Advanced Squamous Cell Lung Cancer Progressed after Platinum-Based Doublet Chemotherapy and Immunotherapy (SPACE Study).
This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and immunotherapy. We recruited patients both retrospectively and prospectively and collected the outcomes and safety data. Additionally, we performed next-generation sequencing using tumor tissue and/or plasma to explore potential molecular biomarkers. Altogether, 42 patients were included in the final analysis. The median number of prior treatments was three (range 1-8), and the median TTF was 2.1 months. Objective response rate and disease control rate were 16.2% and 59.5%, respectively, and median duration of response was 4.0 months among response evaluable patients ( = 37). Treatment-related adverse events (TRAEs, including diarrhea, stomatitis, and paronychia) occurred in 22 (52.3%) patients; however, most were grade 2 or lower, and only 5 cases were grade 3. TRAEs led to dose modification in 17 (40.5%) and discontinuation in 4 (9.5%) patients. The TTF in patients with mutations was significantly longer than that in patients without (6.8 vs. 2.1 months, = 0.045). Our results highlight that afatinib is a reasonable treatment option in terms of effectiveness and safety, and mutation can be used as a predictive biomarker in clinical settings.
PubMed: 38067272
DOI: 10.3390/cancers15235568 -
Cancer Research and Treatment Apr 2024GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase...
PURPOSE
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
MATERIALS AND METHODS
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
RESULTS
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
CONCLUSION
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; ErbB Receptors; Fluorouracil; Irinotecan; Leucovorin; Neoplasm Recurrence, Local; Rectal Neoplasms
PubMed: 38062706
DOI: 10.4143/crt.2023.1117 -
Supportive Care in Cancer : Official... Dec 2023Anti-epidermal growth factor receptor (EGFR) antibodies often cause skin toxicities. Preemptive skin treatments using systemic antibiotics with or without topical...
Evaluation of the additional prophylactic effect of topical steroid ointment to systemic minocycline against anti-epidermal growth factor antibody-induced skin toxicities in metastatic colorectal cancer treatment.
BACKGROUND
Anti-epidermal growth factor receptor (EGFR) antibodies often cause skin toxicities. Preemptive skin treatments using systemic antibiotics with or without topical steroid are reportedly effective although the most suitable method remains unclear. This study aimed to determine whether combination prophylaxis using systemic minocycline and topical steroid is superior to minocycline alone in a real-world metastatic colorectal cancer (mCRC) treatment.
METHODS
Patients with mCRC (n = 87) who received anti-EGFR monoclonal antibodies were retrospectively assessed. The primary objective was to compare the incidence of grade ≥ 2 overall skin toxicities during all treatment periods between the control group receiving prophylactic minocycline 100 mg/day, and the combination prophylaxis group receiving minocycline 100 mg/day + topical steroid. The incidence of each skin symptom was also evaluated.
RESULTS
The incidence of grade ≥ 2 overall skin toxicities was 63.6% in the control and 56.9% in the combination groups, with no significant difference (P = 0.63). Similarly, the incidence of grade ≥ 2 dry skin, fissures, paronychia, and pruritus did not significantly differ. In addition, incidence of all-grade skin toxicities was not different. However, the incidence of grade ≥ 2 papulopustular rashes was significantly lower in the combination group (23.1% vs. 50.0%, P = 0.03). Propensity score-matched analysis supported these results. Multivariate logistic regression analysis showed no significant association between combination prophylaxis and grade ≥ 2 overall skin toxicities, but it did show a reduction in grade ≥ 2 papulopustular rashes.
CONCLUSION
Adding topical steroids to systemic minocycline did not mitigate grade ≥ 2 overall skin toxicities induced by anti-EGFR antibodies; however, it significantly improved papulopustular rashes.
Topics: Humans; Minocycline; Ointments; Retrospective Studies; Skin Diseases; Exanthema; Steroids; Colonic Neoplasms; Intercellular Signaling Peptides and Proteins
PubMed: 38055053
DOI: 10.1007/s00520-023-08195-3 -
JTO Clinical and Research Reports Dec 2023Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The...
A Phase 2 Single-Arm Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis NSCLC: Results for the First-Line Cohort of the OCEAN Study (LOGIK 1603/WJOG 9116L).
INTRODUCTION
Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with mutation. Here, we report the results of the first-line cohort.
METHODS
Previously untreated patients with RT-naive CNS metastasis and mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points.
RESULTS
A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%).
CONCLUSIONS
These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting.
TRIAL REGISTRATION
UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.
PubMed: 38046380
DOI: 10.1016/j.jtocrr.2023.100587 -
Journal of the European Academy of... Mar 2024Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the... (Review)
Review
Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.
Topics: Humans; Onychomycosis; Terbinafine; Itraconazole; Treatment Outcome; Paronychia
PubMed: 38010049
DOI: 10.1111/jdv.19644 -
Cancer Mar 2024Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer...
BACKGROUND
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.
METHODS
In this single-arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment.
RESULTS
Thirty-seven patients started treatment, with a median age of 65 years (range, 40-80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression-free survival was 5.5 months (95% CI, 3.7-8.3 months) and median overall survival was 16.8 months (95% CI, 10.7-25.8 months). The most common treatment-related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients.
CONCLUSIONS
Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.
Topics: Humans; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Carcinoma, Non-Small-Cell Lung; Afatinib; Cetuximab; Lung Neoplasms; ErbB Receptors; Antineoplastic Combined Chemotherapy Protocols; Exons; Mutation; Protein Kinase Inhibitors
PubMed: 37905752
DOI: 10.1002/cncr.35090