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Journal of Oncology 2021The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor...
INTRODUCTION
The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations based on real-world evidence.
MATERIALS AND METHODS
Eligible real-world studies were identified from PubMed, Cochrane Library, and Embase. Cochrane guidelines were used to assess the quality of included studies. Cochran's test and I statistics were used for the heterogeneity analysis.
RESULTS
Twenty-five studies were included in this meta-analysis; nine studies were included in the qualitative descriptive analysis. The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months. The total incidences of adverse events (AEs) for skin rashes, diarrhea, paronychia, and mucositis were 71.4% (64.4%, 77.9%), 70.4% (60.1%, 79.8%), 52.1% (41.9, 62.3%), and 36.5% (29.5%, 43.8%), respectively. The incidences of severe adverse events (SAEs, Grade ≥3) for diarrhea, skin rashes, paronychia, and mucositis were 9.7% (6.8%, 13.1%), 5.8% (4.5%, 7.2%), 3.8% (2.0%, 6.2%), and 2.1% (1.0%, 3.6%), respectively. Differences in PFS and OS between the afatinib non-full-dose (<40 mg) and full-dose (>40 mg) groups were not significant ( > 0.05). However, the ORR in the full-dose group was 78.5% (66.7%, 88.4%), which was significantly higher than that in the non-full-dose group (67.8% [56.8%, 77.9%]).
CONCLUSION
The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results. In real-world setting, tolerability-guided dose adjustment might not affect the afatinib efficacy.
PubMed: 34961817
DOI: 10.1155/2021/8736288 -
Skin Appendage Disorders Nov 2019Cutaneous manifestations of tuberculosis (TB) are rare, particularly from an exogenous source. Involvement of the nail apparatus is extremely rare and has only...
Cutaneous manifestations of tuberculosis (TB) are rare, particularly from an exogenous source. Involvement of the nail apparatus is extremely rare and has only previously been reported as a secondary involvement. We report the case of a 76-year-old female patient referred to our department with onychodystrophy with purulent drainage of the first left finger, which had developed during the preceding year. She had no previous traumatic history and had received treatment with multiple cycles of oral antibiotics and antimycotics, with no clinical improvement. Physical examination showed paronychia and onychodystrophy of the entire nail plate. Biopsy evaluation revealed epithelioid granulomas with central foci of necrosis, and laboratory cultures were positive for complex. Chest computed tomography excluded primary pulmonary TB. X-ray of the left hand revealed the presence of dactylitis on the distal phalanx. Based on these findings, the patient was treated with rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months and with rifampicin and isoniazid for 7 months, resulting in complete resolution of the lesions. Cutaneous TB is a diagnostic challenge, particularly in rare cases such as involvement of the nail apparatus. It should be considered as a diagnostic hypothesis in cases of painless paronychia with refractory purulent drainage and associated onychodystrophy.
PubMed: 31799269
DOI: 10.1159/000501698 -
European Journal of Medical Research Aug 2023The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
METHODS
We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs).
RESULTS
A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies.
CONCLUSIONS
Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Prospective Studies; Antineoplastic Agents; ErbB Receptors; Protein Kinase Inhibitors; Mutation
PubMed: 37542339
DOI: 10.1186/s40001-023-01219-y -
Pharmaceuticals (Basel, Switzerland) Jul 2022Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest... (Review)
Review
Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest studies has been published. We conducted this meta-analysis to evaluate the effectiveness and safety of trametinib in treating NF1-related nerve tumors. Original articles reporting the efficacy and safety of trametinib in NF1 patents were identified in PubMed, EMBASE, and Web of Science up to 1 June 2022. Using R software and the 'meta' package, the objective response rates (ORRs) and disease control rates (DCRs) were calculated to evaluate the efficacy, and the pooled proportion of adverse events (AEs) was calculated. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Eight studies involving 92 patients were included, which had a very low to moderate quality of evidence. The pooled ORR was 45.3% (95% CI: 28.9-62.1%, I = 0%), and the DCR was 99.8% (95% CI: 95.5-100%, I = 0%). The most common AEs was paronychia, with a pooled rate of 60.7% (95% CI: 48.8-72.7%, I = 0%). Our results indicate the satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors of trametinib in NF1-related nerve tumors. The safety profile of trametinib is satisfactory.
PubMed: 36015104
DOI: 10.3390/ph15080956 -
Indian Dermatology Online Journal 2020Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by pustules and/or papillomatous vegetations, preferentially affecting intertriginous and...
Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by pustules and/or papillomatous vegetations, preferentially affecting intertriginous and periorificial areas. It has two subtypes: Hallopeau variant and Neumann variant. Cerebriform tongue, a morphology with typical pattern of sulci and gyri over dorsum of the tongue, is a well-known sign in pemphigus vegetans. We are presenting an unusual case of pemphigus vegetans with extensive involvement of mucosae, trunk, extremities including both extensors and flexural areas with verrucous paronychia and fissured tongue. During clinical exam we recognized multiple cutaneous vesicles, erosions and ulcers on mucosal sites. Clinical, histopathological, and direct and indirect immunofluorescence findings were compatible with pemphigus vegetans. Patient had completed her family so treated with intravenous dexamethasone-cyclophosphamide pulse (DCP) regimen with excellent response.
PubMed: 32055517
DOI: 10.4103/idoj.IDOJ_83_19 -
Clinical Cancer Research : An Official... Apr 2022EGFR pathway inhibition may promote anti-programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen...
PURPOSE
EGFR pathway inhibition may promote anti-programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti-PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment.
PATIENTS AND METHODS
The ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx.
RESULTS
From January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib-pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell-mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy.
CONCLUSIONS
Afatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment.
Topics: Afatinib; Antibodies, Monoclonal, Humanized; Carcinoma, Squamous Cell; ErbB Receptors; Head and Neck Neoplasms; Humans; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 35046059
DOI: 10.1158/1078-0432.CCR-21-3025 -
European Journal of Case Reports in... 2024In rare dermatology cases the differential diagnosis is challenging, e.g. when one nail is growing below another, the provisional diagnosis could be confusing. It may...
BACKGROUND
In rare dermatology cases the differential diagnosis is challenging, e.g. when one nail is growing below another, the provisional diagnosis could be confusing. It may present as chronic paronychia, candidiasis, bacterial infections, rheumatoid arthritis, psoriasis, subungual tumours, or cysts.
CASE DESCRIPTION
We present a case of iatrogenic rupture of the nails of both big toes following a commonly known recommendation from physiotherapists in the initial stages of hallux valgus or chronic arthritis by using kinesio tape to prevent the big toe from fixation in the valgus position. The initial provisional diagnosis of retronychia was revised, and a final diagnosis of onychomadesis was made. The patient's complaint was solved after around one year without any specific therapy.
CONCLUSION
The differential diagnosis for onychomadesis needs a careful and detailed history that may prevent a patient from a frightening diagnosis and painful, long-lasting treatments.
LEARNING POINTS
The differential diagnosis of retronychia, onychomycosis and onychomadesis is challenging.Both onychomadesis and retronychia share a common pathophysiologic mechanism.A careful and detailed history prevents a patient from a frightening diagnosis and painful, long-lasting treatment of nail disorders.
PubMed: 38455698
DOI: 10.12890/2024_004326 -
Journal of the West African College of... 2022Glomus tumours are benign neoplasms arising from the glomus body, a network of specialized neuromyoarterial structures containing arteriovenous anastomosis and...
INTRODUCTION
Glomus tumours are benign neoplasms arising from the glomus body, a network of specialized neuromyoarterial structures containing arteriovenous anastomosis and regulating temperature. It is often misdiagnosed as paronychia, arthritis, traumatic sequelae, and many other conditions including psychiatric misdiagnosis. A typical triad of paroxysmal pain, point tenderness, and cold intolerance characterize it. Surgical excision is the treatment of choice, either by transungual or lateral approaches.
MATERIALS AND METHODS
We carried out a retrospective study of cases operated in our department in the last 4 years. Patients are evaluated based on either clinical parameters (Love test, Hildreth test, and cold insensitivity) or radiological parameters (X-ray and magnetic resonance imaging). Parameters such as age, gender, tumour side, presenting complaints, duration of symptoms, diagnostic modality, follow-up duration, recurrence, and postoperative nail deformity were analysed. Visual analogue scale (VAS) score was the primary statistical parameter, and the change in VAS score following surgery was analysed with paired test.
RESULT
Mean preoperative VAS was 7.75 ± 0.5; in a total of four patients, and following surgery, VAS was reduced to a mean of 1 ± 1.5. Paired test on the change of VAS score following surgery showed a significant difference in the VAS score ( = 0.002838). The average age was 39.25. The male-to-female ratio was 1:3, and the mean follow-up was 16 months (range 2-48 months). The mean duration of symptoms was 5.75 years (range 2-10 years). Two cases were in the right-hand side, and two cases were on the left-hand side; the thumb was most commonly involved with 50% ( = 2) incidence.
CONCLUSION
Glomus tumours are often misdiagnosed and are intervened with different treatment options before being surgically intervened. With complete surgical excision, recurrence is nil but postoperative nail growth requires nearly 10 months.
LEVEL OF EVIDENCE
Level IV.
PubMed: 36590779
DOI: 10.4103/jwas.jwas_171_22 -
Cureus Jul 2022Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor on T-cells and blocks its interaction with PD-L1 and PD-L2, releasing...
Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor on T-cells and blocks its interaction with PD-L1 and PD-L2, releasing the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response, resulting in decreased tumor growth. Here, we present a case of a 56-year-old lady with a diagnosis of squamous cell carcinoma (SCC) of the lip who presented with dystrophy of 20 nails, distal onycholysis, yellow-black discoloration of nail plates, painful paronychia with superimposed bacterial infection of big toes of both feet for three months. Few warty growths were also appreciated on big toes of both feet. She had undergone for her SCC 33 sessions of radiotherapy and 43 cycles of nivolumab 140mg for 60 minutes every two weeks. Following discontinuing this drug, the peri-ungual and nail bed inflammation improved, however nail plate dystrophy persisted. To our knowledge, the occurrence of nail dystrophy with nivolumab has never been reported before but it has been described with other targeted therapies.
PubMed: 35989738
DOI: 10.7759/cureus.26950 -
Scientific Reports Jul 2022Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians' suggestions on nail care recommendations based on the patients' needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient's decisions are warranted.
Topics: Breast Neoplasms; Female; Humans; Middle Aged; Nail Diseases; Onycholysis; Quality of Life; Taxoids
PubMed: 35798751
DOI: 10.1038/s41598-022-13327-6