-
Cancers Oct 2023Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second...
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).
Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
PubMed: 37894366
DOI: 10.3390/cancers15204999 -
BMC Cancer Oct 2023About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to...
BACKGROUND
About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC.
METHODS
Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.
RESULT
Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs.
CONCLUSIONS
Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cohort Studies; Antineoplastic Agents; Protein Kinase Inhibitors; ErbB Receptors; Mutation
PubMed: 37840124
DOI: 10.1186/s12885-023-11465-2 -
Indian Dermatology Online Journal 2023
PubMed: 37727563
DOI: 10.4103/idoj.idoj_527_22 -
Clinical and Experimental Dermatology Oct 2023Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity,...
Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs. The pathogenesis of EGFRI-induced EPDS is poorly understood. Here we present three cases of EPDS induced by EGFRIs. The proteins LTA4H (leukotriene A-4 hydrolase), METAP1 (methionine aminopeptidase 1), BID (BH3-interacting domain death agonist), SMAD1 (mothers against decapentaplegic homologue), PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A), YES1 (tyrosine-protein kinase Yes) and EGFL7 (epidermal growth factor-like protein 7) were significantly upregulated in EGFRI-stimulated peripheral blood mononuclear cell cultures, and validated in the lesions. All of the proteins colocalized with CD4+ and CD8+ T-cell expression. Next-generation-based human leucocyte antigen (HLA) typing showed all patients carried HLA-C*15:02, and modelling studies showed that afatinib and erlotinib bound well within the E/F binding pockets of HLA-C*15:02. Moreover, T cells were preferentially activated by EGFRIs in individuals carrying HLA-C*15:02. The case series revealed that EGFRI-induced EPDS may be mediated by drug-specific T cells.
Topics: Humans; Scalp; HLA-C Antigens; Leukocytes, Mononuclear; Skin Diseases; Exanthema; ErbB Receptors; Aminopeptidases; Calcium-Binding Proteins; EGF Family of Proteins
PubMed: 37710038
DOI: 10.1093/ced/llad282 -
Cureus Sep 2023Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative,...
Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management. Methods This observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee. Results Among the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes. Conclusions Beyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.
PubMed: 37701161
DOI: 10.7759/cureus.45007 -
Journal of Pediatric OrthopedicsDistinguishing the severity of the diagnosis and an appropriate treatment plan in pediatric hand infections can be complex due to the variable amount of information...
INTRODUCTION
Distinguishing the severity of the diagnosis and an appropriate treatment plan in pediatric hand infections can be complex due to the variable amount of information available at the presentation. Inflammatory blood markers, including white blood cell count, erythrocyte sedimentation rate, and C-reactive protein are reported to aid in determining the severity of infection and response to treatment in adult hand infections. The purpose of this study was to identify the relevance of inflammatory marker levels in pediatric patients with hand and wrist infections and to determine their utility in diagnosis and treatment.
METHODS
This multicenter, retrospective, cohort study included patients aged 0 to 18 who received treatment for an acute hand or wrist infection between 2009 and 2020. Data collected included demographics, time to presentation, diagnosis, inflammatory markers, culture results, antibiotic treatment, and surgical treatment. Infections were categorized as deep (osteomyelitis, tenosynovitis, abscess) and superficial (paronychia, felon, cellulitis). Exclusion criteria included: patients above 18 years of age, chronic infection, open fractures, and absence of any documented inflammatory markers. Statistically, t tests were used to compare mean differences in inflammatory markers between patients who did and did not receive pretreatment antibiotics and between patients who had superficial versus deep hand infections.
RESULTS
A total of 123 patients met the inclusion criteria. Pretreatment with antibiotics before definitive management was not significantly associated with differences in laboratory markers compared with patients not pretreated with antibiotics. Deep hand infections had inflammatory markers similar to superficial infections. Patients with deep hand infections required a bedside or operative procedure 78.9% of the time compared with superficial infections (21.2%) ( P <0.001). Patients with an isolated methicillin-resistant Staphylococcus aureus infection had inflammatory marker values that were not significantly different from patients infected with all other microbes.
CONCLUSIONS
Inflammatory markers were not significantly different between patients who received pretreatment with antibiotics and those who did not. While deep infections were often treated with bedside or surgical procedures, the inflammatory marker values were similar to those of superficial infections. The same held true for patients infected with culture-positive, isolated methicillin-resistant Staphylococcus aureus bacteria. Consequently, inflammatory markers may be useful to identify the presence of infection and monitor the response to treatment, they did not aid in determining the specific type of infection or selection of a treatment plan.
LEVEL OF EVIDENCE
Level III-retrospective comparative study.
Topics: Adult; Humans; Child; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Cohort Studies; Staphylococcal Infections; Infections; Abscess; Anti-Bacterial Agents
PubMed: 37678156
DOI: 10.1097/BPO.0000000000002508 -
Lung Cancer (Amsterdam, Netherlands) Oct 2023Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment.
PATIENTS AND METHODS
Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group). The primary endpoint was PFS. The power was >50% under the assumptions of a median PFS of 12 months for the Afa group and hazard ratio (HR) of 0.6 for the AfaBev group.
RESULTS
Between August 2017 and September 2019, 100 patients were enrolled. There was no significant difference in PFS between the groups. The median PFS was 16.3 and 16.1 months for the AfaBev and Afa groups, respectively, with an HR of 0.865 (95% confidence interval [CI], 0.539 to 1.388; p = 0.55). In terms of overall survival, there was no significant difference between the groups (HR, 0.84; 95% CI, 0.39 to 1.83; p = 0.67). The overall response rate was 82.6% and 76.6% in the AfaBev and Afa groups, respectively (p = 0.61). Grade ≥ 3 diarrhea, hypertension, acneiform rash, paronychia, and stomatitis were frequently observed in the AfaBev group.
CONCLUSIONS
This study failed to show efficacy of AfaBev over Afa for improving PFS in untreated patients with EGFR-mutated NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Afatinib; Bevacizumab; Lung Neoplasms; ErbB Receptors; Mutation
PubMed: 37651927
DOI: 10.1016/j.lungcan.2023.107349 -
The Journal of Dermatology Dec 2023Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of... (Review)
Review
Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of onychomycosis caused by Fusarium spp., it is characterized by drug sensitivity and other characteristics. Here, we report what may be the first case of onychomycosis caused by Fusarium lactis. We analyzed the mycology and characterized previously reported cases of onychomycosis caused by Fusarium spp. A 73-year-old otherwise healthy woman presented with discoloration and thickening of her right thumbnail with paronychia. Direct microscopy revealed unevenly swollen hyphae, and a Grocott-stained nail specimen showed septate hyphae. Based on the morphological features and gene analysis of fungus isolated from the nail, we diagnosed onychomycosis caused by F. lactis belonging to Fusarium fujikuroi species complex. Partial nail removal and topical application of 1% luliconazole solution resolved the condition in 6 months. Minimum inhibitory concentrations for isolated F. lactis showed high sensitivity to luliconazole but not itraconazole or terbinafine. The isolated F. lactis was temperature-sensitive. A search of the literature revealed 57 cases of onychomycosis caused by Fusarium spp. with delineated clinical characteristics. Since those cases were investigated using morphological and/or molecular methods, we analyzed them by species complex as well as species. Onychomycosis caused by Fusarium spp. is predominantly found on the big toe, with Fusarium solani species complex and Fusarium oxysporum species complex accounting for over 70% of cases. Infection of only one digit with paronychia is a characteristic clinical manifestation of onychomycosis caused by Fusarium spp. Since there has been an increase in instances of molecular determination of Fusarium spp., it is deemed necessary to clarify its clinical and fungal nature. Due to its characteristic drug sensitivity and temperature-sensitive nature, new treatments are expected to be developed.
Topics: Aged; Female; Humans; Antifungal Agents; Fusarium; Naphthalenes; Onychomycosis; Paronychia
PubMed: 37622410
DOI: 10.1111/1346-8138.16931 -
JACC. CardioOncology Aug 2023•Mutations in the gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous mutations,... (Review)
Review
•Mutations in the gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation. Common side effects include acneiform rash, diarrhea, and paronychia. Osimertinib has also been associated with cardiomyopathy (∼1.4%-2.4%) and prolongation of the QT interval (2.7%).•In our experience, osimertinib-induced cardiomyopathy can be managed with the cessation of osimertinib and the initiation of guideline-directed therapy. Given that osimertinib is often the best available therapy, rechallenging with osimertinib often favors benefit over risk. Safe rechallenge with osimertinib is demonstrated in this case.
PubMed: 37614580
DOI: 10.1016/j.jaccao.2023.04.005 -
The Journal of Foot and Ankle Surgery :... 2023To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to...
To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to August 2021 were treated with Ω toenail correction according to clinical stages, the clinical therapeutic effects of which were evaluated in terms of the operation time, the time to resume movement, treatment cycle, 1-y recurrence rate, and visual analogue scale (VAS) scores before and after treatment. The clinical efficacy was analyzed and compared of Ω toenail correction in treating paronychia of different clinical stages. It has been demonstrated that there was no significant difference in operation time, time to resume movement, treatment cycle and recurrence rate among different stages of paronychia, while there existed the significant difference (p < .05) in VAS score of resting-state pain before and after correction which stood at 6.43 ± 0.29 points with the after-treatment VAS scores at 1.10 ± 0.22. There is a statistical difference (p < .05) in VAS score of movement-evoked pain between before and after treatment. The VAS scores of movement-evoked pain stood at 7.55 ± 0.42, which is in contrast with the after-treatment VAS at 1.74 ± 0.93. It has been concluded that Ω toenail correction characterized by easy operation can relieve the pain immediately, which can achieve satisfactory clinical efficacy for treating paronychia of different stages.
Topics: Humans; Female; Male; Middle Aged; Paronychia; Adult; Treatment Outcome; Nails; Pain Measurement; Aged; Retrospective Studies; Operative Time
PubMed: 37580011
DOI: 10.1053/j.jfas.2023.05.010