-
JAMA Otolaryngology-- Head & Neck... May 2024There is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration.
IMPORTANCE
There is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration.
OBJECTIVE
To examine the efficacy, safety, and tolerability of vascular endothelial growth factor receptor (VEGFR) inhibitors in recurrent or metastatic ACC.
DATA SOURCES
PubMed, Embase, and Cochrane Library were systematically searched for studies of VEGFR inhibitors in recurrent or metastatic ACC from database inception to August 31, 2023.
STUDY SELECTION
Inclusion criteria were prospective clinical trials of recurrent or metastatic ACC treated with VEGFR inhibitors, reporting at least 1 outcome of interest specifically for ACC. Of 1963 identified studies, 17 (0.9%) met inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% CIs.
MAIN OUTCOMES AND MEASURES
The primary efficacy outcome was best overall response to VEGFR inhibitors, including objective response, stable disease, or progressive disease (PD). Safety and tolerability outcomes included incidence of grade 3 or higher adverse events, rates of exit from trial due to PD or drug-related toxic effects, and dose reduction rate (DRR).
RESULTS
A total of 17 studies comprising 560 patients with recurrent or metastatic ACC treated with 10 VEGFR inhibitors were included. The objective response rate was 6% (95% CI, 3%-12%; I2 = 71%) and stable disease was the most frequent best overall response (82%; 95% CI, 74%-87%; I2 = 67%). The 6-month disease control (defined as objective response and stable disease) rate was 54% (95% CI, 45%-62%; I2 = 52%). The rate of grade 3 or higher adverse events was 53% (95% CI, 42%-64%; I2 = 81%) and of DRR was 59% (95% CI, 40%-76%). Most patients (57%; 95% CI, 44%-70%; I2 = 83%) continued therapy until PD; 21% (95% CI, 15%-28%; I2 = 62%) of patients suspended therapy for toxic effects. In subgroup analysis by specific VEGFR inhibitor, the objective response rate was 14% (95% CI, 7%-25%; I2 = 0%), stable disease rate was 76% (95% CI, 63%-85%; I2 = 0%), proportion treated until PD was 61% (95% CI, 14%-94%; I2 = 94%), and DRR was 78% (95% CI, 66%-87%; I2 = 39%) with lenvatinib. Corresponding axitinib results were objective response rate of 8% (95% CI, 4%-15%; I2 = 0%) and stable disease rate of 85% (95% CI, 72%-92%; I2 = 69%), with 73% (95% CI, 63%-82%; I2 = 0%) of patients treated until PD, and the DRR was 22% (95% CI, 12%-38%; I2 = 77%). Rivoceranib had the highest objective response rate (24%; 95% CI, 7%-57%) but high heterogeneity among studies (I2 = 95%) and the lowest rate of patients who continued therapy until PD (35%; 95% CI, 20%-55%; I2 = 90%).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that VEGFR inhibitors were associated with high rates of disease stabilization in recurrent or metastatic ACC. Of 10 included VEGFR inhibitors, lenvatinib and axitinib were associated with the best combined and consistent efficacy, safety, and tolerability profiles, substantiating their inclusion in treatment guidelines.
PubMed: 38814585
DOI: 10.1001/jamaoto.2024.1177 -
Journal of Oral and Maxillofacial... 2024c-KIT is an important diagnostic marker in salivary gland tumours and is expressed in most adenoid cystic carcinomas. Histologically similar salivary gland tumours with... (Review)
Review
c-KIT is an important diagnostic marker in salivary gland tumours and is expressed in most adenoid cystic carcinomas. Histologically similar salivary gland tumours with variable immunohistochemical expression for c-KIT pose a challenge and make diagnostic reliability ambivalent. An electronic search was performed in MEDLINE by PubMed, Google Scholar, Scopus, Trip, Cochrane Library, and EMBASE up to 31 December 2023, without period restriction. The articles that investigated CD117 or c-KIT in salivary gland tumours were included for review. Sensitivity, specificity, and positive and negative predictive values of c-KIT immunohistochemical expressions were derived and subjected to meta-analysis using Open Meta analyst for Sierra software. The risk of bias in selected studies was analysed using the QUADAS-2 tool, and RevMan 5.4 was used to output the result. Forty-three articles were reviewed, and 2285 salivary gland cases were analysed. Adenoid cystic carcinoma had an overall expression of 84.9%. A similar expression was found in epimyoepithelial carcinoma (79.1%), lymphoepithelial carcinoma (75%), myoepithelial carcinoma (60.8%), monomorphic adenoma (94.1%), and pleomorphic adenoma (74.7%). The sensitivity, specificity, and positive and negative predictive values of c-KIT/CD117 for adenoid cystic carcinoma with other salivary gland tumours were 84.99%, 69.09%, 84.79%, and 69.41%, respectively. Current evidence shows that c-KIT, despite its sensitivity, is not specific and therefore cannot be a useful diagnostic marker for distinguishing adenoid cystic carcinoma from other salivary gland tumours. Further research on other salivary gland tumours that exhibit comparable expression is necessary to validate the diagnostic accuracy of c-KIT.
PubMed: 38800447
DOI: 10.4103/jomfp.jomfp_70_24 -
Technology in Cancer Research &... 2024Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential... (Meta-Analysis)
Meta-Analysis
Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.
Topics: Humans; Carcinoma, Adenoid Cystic; Head and Neck Neoplasms; Proton Therapy; Heavy Ion Radiotherapy; Treatment Outcome
PubMed: 38773763
DOI: 10.1177/15330338241246653 -
Gastroenterology Research Apr 2024Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and...
BACKGROUND
Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model.
RESULTS
Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I = 0%).
CONCLUSIONS
In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.
PubMed: 38716286
DOI: 10.14740/gr1672 -
Clinical Otolaryngology : Official... Jul 2024Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H.
METHODS
Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children.
RESULTS
Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]).
CONCLUSIONS
The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.
Topics: Humans; Adenoids; Cyclopropanes; Quinolines; Acetates; Sulfides; Hypertrophy; Child; Mometasone Furoate; Leukotriene Antagonists; Administration, Intranasal; Drug Therapy, Combination; Treatment Outcome
PubMed: 38700144
DOI: 10.1111/coa.14169 -
Clinical Pharmacokinetics Apr 2024Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and...
BACKGROUND AND OBJECTIVE
Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population.
METHODS
A systematic literature search was performed in the MEDLINE and Embase databases.
RESULTS
Forty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1-93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited.
CONCLUSION
The influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.
Topics: Humans; Child; Tissue Distribution; Infant; Child, Preschool; Infant, Newborn; Adolescent; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 38551787
DOI: 10.1007/s40262-024-01364-5 -
International Journal of Ophthalmology 2024To evaluate lacrimal gland adenoid cystic carcinoma (LGACC) of prognosis in patients who underwent different treatment regimens.
AIM
To evaluate lacrimal gland adenoid cystic carcinoma (LGACC) of prognosis in patients who underwent different treatment regimens.
METHODS
We searched PubMed, EMBASE, and the Cochrane Library for studies done on the treatment of LGACC, between January 1987 and April 2022. A Meta-analysis was conducted to pool the 5-year overall survival rate (OR), and the 5-year recurrence rate (RR) and 5-year metastasis rate (MR) were assessed.
RESULTS
The 30 studies involved 585 patients were included in the Meta-analysis. The pooled 5-year OR with surgery alone was 50%, the 5-year RR was 63%, and the 5-year MR was 34%. The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67% (95%CI 61%,73%), the 5-year RR was 41%, and the 5-year MR was 35%. The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72% (95%CI 59%, 84%), the 5-year RR was 48%, and the 5-year MR was 36%. The pooled 5-year OR with surgery, intra-arterial cytoreductive chemotherapy, and adjuvant chemoradiotherapy combined was 78% (95%CI 68%, 89%), the 5-year RR was 15%, and the 5-year MR was 27%.
CONCLUSION
Comprehensive treatment is more effective than surgery alone. Surgery combined with intra-arterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.
PubMed: 38239951
DOI: 10.18240/ijo.2024.01.22 -
Journal of Clinical Medicine Jan 2024Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This... (Review)
Review
BACKGROUND
Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This study aimed to comprehensively review ACC of MSGs, focusing on clinical characteristics, imaging modalities, treatment approaches, and long-term outcomes.
METHODS
A systematic search was conducted in PubMed, Web of Science, and MEDLINE databases to identify relevant articles reporting cases of ACC of MSGs between January 1997 and March 2023. The study was registered in PROSPERO (ID: CRD42023449478). A total of 10 studies that met the inclusion criteria were selected for critical review. In total, 902 patients were diagnosed with ACC of MSGs with an age range of 44.3 to 63 years, and an average age of 56.6 years. The female to male ratio ranges from 1:1 to 2.4:1. Regarding the primary site of ACC, the palate was the most common location, accounting for 30.5% to 83.3%, followed by the buccal mucosa, floor of the mouth, and lip and the retromolar area. For histology, the solid mass pattern was the most prevalent, seen in 95.2% of patients, followed by the cribriform pattern. Regarding treatment modalities, surgery was the most common approach, applied in 76.3% of cases, with a combination of surgery and radiotherapy used in 29.0% of cases. A smaller fraction, 3.2%, received a combination of surgery, chemotherapy, and radiotherapy, and 8.3% underwent radiotherapy alone. Local recurrence rates varied between 1% and 28.5%, and distant metastasis occurred in 18.2% to 33.3% of cases, predominantly to lymph nodes (14.5%). An analysis of overall survival across various stages and patient numbers indicated a 5-year survival rate of 68.0%. The findings of this study provide valuable insights for physicians in making treatment decisions and emphasize the need for ongoing research and collaborative clinical efforts to improve the management and outcomes of this challenging disease.
CONCLUSION
ACC of MSGs is a multifaceted condition typically manifesting as asymptomatic enlargement and ulceration. This disease is marked by distinct histopathological patterns and perineural invasion (PNI). Recognizing these distinctive aspects is key in shaping the treatment plan, which can range from surgical procedures to radiation therapy, chemotherapy, and evolving targeted treatments. Continuous research and collaborative clinical efforts remain critical for ongoing progress in the treatment and management of this challenging condition.
PubMed: 38202273
DOI: 10.3390/jcm13010267 -
Diagnostics (Basel, Switzerland) Jan 2024The purpose of this study was to review the diagnostic accuracy of MRI in detecting perineural spreading (PNS) of head and neck tumors using histopathological or... (Review)
Review
The purpose of this study was to review the diagnostic accuracy of MRI in detecting perineural spreading (PNS) of head and neck tumors using histopathological or surgical evidence from the afflicted nerve as the reference standard. Previous studies in the English language published in the last 30 years were searched from PubMed and Embase databases. We included studies that used magnetic resonance imaging (MRI) (with and without contrast enhancement) to detect PNS, as well as the histological or surgical confirmation of PNS, and that reported the exact numbers of patients required for assessing diagnostic accuracy. The outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed with the Higgins inconsistency test (I). P-values smaller than 0.05 were considered statistically significant. A total of 11 retrospective studies were found, reporting 319 nerve samples from 245 patients. Meta-analytic estimates and their 95% confidence intervals were as follows: sensitivity 0.85 (0.70-0.95), specificity 0.85 (0.80-0.89), PPV 0.86 (0.70-0.94), and NPV 0.85 (0.71-0.93). We found statistically significant heterogeneity for sensitivity (I = 72%, = 0.003) and PPV (I = 70%, = 0.038), but not for NPV (I = 65%, = 0.119) or specificity (I = 12%, = 0.842). The most frequent MRI features of PNS were nerve enlargement and enhancement. Squamous cell carcinoma and adenoid cystic carcinoma were the most common tumor types, and the facial and trigeminal nerves were the most commonly affected nerves in PNS. Only a few studies provided examples of false MRI diagnoses. MRI demonstrated high diagnostic accuracy in depicting PNS of cranial nerves, yet this statement was based on scarce and heterogeneous evidence.
PubMed: 38201423
DOI: 10.3390/diagnostics14010113 -
Sleep & Breathing = Schlaf & Atmung May 2024This study aimed to conduct a meta-analysis and systematic review of drug-induced sleep endoscopy (DISE) in pediatric conventional obstructive sleep apnea-hypopnea... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to conduct a meta-analysis and systematic review of drug-induced sleep endoscopy (DISE) in pediatric conventional obstructive sleep apnea-hypopnea syndrome (OSAHS) without previous upper airway surgery, or comorbidity, to evaluate the change in treatment strategies and to identify obstructive sites observed during DISE. This study aimed to explore the role of DISE in the management of pediatric conventional OSAHS.
METHODS
A comprehensive search was conducted using both computerized and manual methods to retrieve relevant case studies on DISE-guided treatment of pediatric conventional OSAHS from databases including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WF, and VIP database. The search period extended from database inception to January 2023. Strict inclusion and exclusion criteria were applied to select relevant literature, and data extraction was performed accordingly. Meta-analysis was conducted using the Stata 16.0 software.
RESULTS
A total of 761 patients from four studies were included in the meta-analysis. All pediatric patients had no history of upper airway surgery, craniofacial abnormalities, or syndromes other than OSAHS. The quality assessment revealed that the included studies were of low methodological quality and consisted of non-randomized case studies. Meta-analysis results indicated that in pediatric patients with OSAHS, the obstruction rates observed during DISE were as follows: nasopharyngeal (adenoid) obstruction 93%, soft palate obstruction 35%, oropharyngeal (tonsil) obstruction 76%, tongue base obstruction 32%, supraglottic obstruction 31%, and multi-level obstruction 60%. DISE led to a change in the conventional surgical approach in 45% (95% CI: 29-60%) of patients with OSAHS, providing individualized treatment plans. Postoperative symptoms and sleep-related parameters improved significantly compared to preoperative values, with DISE findings possibly enhancing surgical success rates and potentially avoiding unnecessary procedures.
CONCLUSION
In some cases, DISE may potentially lead to alterations in conventional surgical approaches for children with OSAHS who had no history of upper airway surgery, craniofacial abnormalities, or other syndromes.. The results of our meta-analysis were in favor of DISE-directed approach for pediatric conventional OSAHS. However, further high-quality randomized controlled trials (RCTs) are warranted in future research to investigate the role of DISE in the management of pediatric OSAHS.
Topics: Humans; Sleep Apnea, Obstructive; Endoscopy; Child
PubMed: 37917282
DOI: 10.1007/s11325-023-02945-7