-
International Journal of Molecular... Jan 2024Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates... (Review)
Review
Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
Topics: Humans; Ameloblastoma; Craniopharyngioma; Imidazoles; Oximes; Pituitary Neoplasms
PubMed: 38255797
DOI: 10.3390/ijms25020723 -
Medical Oncology (Northwood, London,... Apr 2023Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the... (Review)
Review
BACKGROUND
Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the permanent "on" state and relays the growth-promoting signals independently of the EGFR pathway. Therefore, mutant BRAF represents a target for handful of new drugs.
METHODS
We conducted a literature search, with the search terms "Vemurafenib, Dabrafenib, Ameloblastoma, and BRAF." These included seven case reports with nine patients who underwent monotherapy with Dabrafenib or Vemurafenib or combination therapy with Dabrafenib and Trametinib.
RESULTS
The patients age ranges from 10 years up to 86 years. The distribution of women and men is 4:5. Patients with an initial diagnosis of ameloblastoma, as well as recurrences or metastasized ameloblastoma were treated. Indications cover neoadjuvant therapy up to the use in metastasized patients in an irresectable state. Results ranging from "only" tumor size reduction to restitutio ad integrum.
CONCLUSION
We see the use of BRAF Inhibitors to reduce tumor size with consecutive surgical treatment as a reasonable option for therapy. However, we are aware that at present the data are based only on case reports with the longest follow-up of just 38 months. We encourage further clinical trials in the use of BRAF Inhibitors for selecting ameloblastoma patients in a multi-center setting.
Topics: Male; Humans; Female; Child; Vemurafenib; Proto-Oncogene Proteins B-raf; Ameloblastoma; Imidazoles; Protein Kinase Inhibitors; Mutation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37115331
DOI: 10.1007/s12032-023-01993-z -
Metastasizing Ameloblastoma: A 10 Year Clinicopathological Review with an Insight Into Pathogenesis.Head and Neck Pathology Sep 2021Ameloblastoma, a benign but locally aggressive odontogenic tumor, often demonstrates metastasis despite benign histological features and this variant is termed as...
Ameloblastoma, a benign but locally aggressive odontogenic tumor, often demonstrates metastasis despite benign histological features and this variant is termed as metastasizing ameloblastoma (METAM). It was classified under the malignant category in the 2005 WHO but has been re-classified under benign epithelial odontogenic tumors in the latest 2017 WHO classification. The present review aimed at gathering the available data on METAM to update the current cognizance about the pathology. Comprehensive search of the databases (viz., PubMed, Medline, SCOPUS, Web of Science, EMBASE and Google Scholar) was done for published articles on METAM following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 42 cases were extracted. The mean age of occurrence was 42.71 ± 15.87 years. A slight male predilection was noted. Mandibular cases showed more metastasis than maxillary cases. Follicular ameloblastoma was most frequently encountered at secondary site followed by plexiform type. Lungs were the most commonly affected secondary sites. METAM is a rare odontogenic tumor and the diagnosis is usually made in retrospect. Inadequate treatment may result in multiple recurrences and metastasis in rare instances. Metastasis in ameloblastoma appears to be multi-factorial in nature and needs further investigation in untapped territory like exploration of quantum effects at cellular and molecular levels.
Topics: Adult; Aged; Ameloblastoma; Female; Humans; Jaw Neoplasms; Male; Middle Aged
PubMed: 33394372
DOI: 10.1007/s12105-020-01258-5 -
BMC Oral Health Dec 2023Ameloblastoma (AM), the benign counterpart of ameloblastic carcinoma, is a benign odontogenic tumor of epithelial origin, naturally aggressive, with unlimited growth...
BACKGROUND
Ameloblastoma (AM), the benign counterpart of ameloblastic carcinoma, is a benign odontogenic tumor of epithelial origin, naturally aggressive, with unlimited growth potential and a high tendency to relapse if not adequately removed. Patients with AM treated surgically can benefit from dental implant therapy, promoting oral rehabilitation and improving their quality of life. The present study aimed to determine the survival rate of dental implants placed after surgical treatment of patients affected by AM. In addition, there were two secondary objectives: 1) To evaluate which dental implant loading protocols are most frequently used and 2) To determine the type of prosthetic restoration most commonly used in these patients.
METHODS
The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed during the study. Searches were performed in three databases (PubMed/MEDLINE, Scopus, and Google Scholar) until November 2023. Additionally, the electronic search was enriched by an iterative hand search of journals related to oral pathology and medicine, maxillofacial surgery, and oral prosthodontics and implantology. Only reports and case series in English from January 2003 to date were included. The Joanna Briggs Institute tool (JBI-Case Reports/Case Series) was used for the study quality assessment.
RESULTS
The total number of patients and implants studied were 64 and 271, respectively, all with surgically treated AM. The patient's ages ranged from 8 to 79 years, with a mean (SD) age of 37.3 ± 16.4. Fifty-three percent were male and 47% were female. The range of follow-up duration was 1 to 22 years. An implant survival/success rate of 98.1% was reported. In addition, most of them were conventionally loaded (38.3%). Hybrid implant-supported fixed dentures were the most commonly used by prosthodontists (53%).
CONCLUSIONS
Oral rehabilitation with dental implants inserted in free flaps for orofacial reconstruction in surgically treated patients with AM can be considered a safe and successful treatment modality.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Ameloblastoma; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis, Implant-Supported; Dental Restoration Failure; Neoplasm Recurrence, Local; Odontogenic Tumors; Quality of Life; Treatment Outcome
PubMed: 38110933
DOI: 10.1186/s12903-023-03765-7 -
World Journal of Clinical Oncology Jan 2020Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different...
BACKGROUND
Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.
AIM
To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors.
METHODS
An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed.
RESULTS
Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E.
CONCLUSION
The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
PubMed: 31976308
DOI: 10.5306/wjco.v11.i1.31