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EJNMMI Research Apr 2024A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation....
BACKGROUND
A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto pretreatment in an open-label, randomized cross-over order. Entresto was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.
RESULTS
Pretreatment with Entresto showed no additional toxicity and increased the stability of [Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto.
CONCLUSIONS
Premedication with Entresto results in a relevant stabilization of [Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs. Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018.
PubMed: 38581480
DOI: 10.1186/s13550-024-01101-w -
Frontiers in Oncology 2024Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary... (Review)
Review
Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as , , , , , , and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.
PubMed: 38571492
DOI: 10.3389/fonc.2024.1286426 -
Frontiers in Genetics 2024Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in . Splice site variants (SSV) reflect changes in mRNA processing,...
Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC. The prevalence of SSVs was evaluated in 3,624 cases with next generation sequence reports, including 25 MTCs. Fisher exact analysis was performed to compare SSV frequency in cancers with/without a diagnosis of MTC. All 25 MTCs had at least one of the two most common SSVs versus 0.3% of 3,599 cancers with other diagnoses ( < 0.00001). The 11 cancers with non-MTC diagnoses that had the common SSVs were 4 neuroendocrine cancers, 4 non-small cell lung carcinomas, 2 non-MTC thyroid cancers, and 1 melanoma. All 25 MTCs analyzed had at least one of the two most common SSVs, including 4 with no identified mutational driver. The identification of SSVs in all MTCs, but rarely in other cancer types, demonstrates that these SSVs distinguish MTCs from other cancer types. Future studies are needed to investigate whether these SSVs play a pathogenic role in MTC.
PubMed: 38566816
DOI: 10.3389/fgene.2024.1377158 -
Cureus Mar 2024Multiple Endocrine Neoplasia type 2B (MEN2B) is an autosomal dominant cancer syndrome caused by a mutation in rearranged during transfection (RET) proto-oncogene and...
Multiple Endocrine Neoplasia type 2B (MEN2B) is an autosomal dominant cancer syndrome caused by a mutation in rearranged during transfection (RET) proto-oncogene and includes medullary thyroid carcinoma, pheochromocytoma, gastrointestinal neuromas, and mucosal ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN2B syndrome. Medullary thyroid carcinoma can often appear during the first years of life. While mucosal neuromas in MEN2B are common, laryngeal neuromas are extremely rare. We present a third case of a pediatric patient with a laryngeal neuroma localized to the left true vocal cord and conduct a literature review of vocal cord neuromas in MEN2B patients.
PubMed: 38562350
DOI: 10.7759/cureus.55406 -
BMC Medical Imaging Mar 2024Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide...
BACKGROUND
Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC.
METHODS
We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student's t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong's test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models.
RESULTS
The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM.
CONCLUSIONS
We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.
Topics: Humans; Retrospective Studies; Lymphatic Metastasis; Radiomics; Thyroid Neoplasms; Lymph Nodes; Carcinoma, Neuroendocrine
PubMed: 38500053
DOI: 10.1186/s12880-024-01222-7 -
Endokrynologia Polska 2024Not required for Clinical Vignette.
Not required for Clinical Vignette.
Topics: Humans; Adrenocorticotropic Hormone; Carcinoma, Neuroendocrine; Cushing Syndrome; Thyroid Neoplasms
PubMed: 38497400
DOI: 10.5603/ep.96863 -
BMC Oral Health Mar 2024Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic... (Clinical Trial)
Clinical Trial
Performance of cone-beam computed tomography (CBCT) in comparison to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone invasion in oral squamous cell cancer (OSCC): a prospective study.
BACKGROUND
Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC.
METHODS
We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities.
RESULTS
Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI.
CONCLUSION
Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.
Topics: Humans; Carcinoma, Squamous Cell; Cone-Beam Computed Tomography; Epithelial Cells; Head and Neck Neoplasms; Magnetic Resonance Imaging; Mouth Neoplasms; Prospective Studies; Spiral Cone-Beam Computed Tomography; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed
PubMed: 38493083
DOI: 10.1186/s12903-024-04057-4 -
Ear, Nose, & Throat Journal Mar 2024Thyroid carcinoma with cutaneous metastases is a rare clinical finding. Cutaneous metastases from thyroid carcinoma have been associated with a poor prognosis, but... (Review)
Review
Thyroid carcinoma with cutaneous metastases is a rare clinical finding. Cutaneous metastases from thyroid carcinoma have been associated with a poor prognosis, but these data are limited to case reports. The exact mechanism of cutaneous metastases from thyroid carcinoma is not clear. Our study aims to report the demographic, clinical, and histologic findings of patients with cutaneous metastases from thyroid carcinoma. A review was conducted using the Medline/PubMed, Cochrane, and Scopus databases to review literature from inception to May 2023. Data extracted included patient age at diagnosis of cutaneous metastases, patient sex, thyroid carcinoma histotype, location of metastases, the time interval between diagnoses of thyroid carcinoma and cutaneous metastases, and overall survival (OS) from the time of cutaneous metastases. One hundred thirty-six patients were identified and 75 were female. The most common types of thyroid carcinoma with cutaneous metastases were papillary (47.79%), followed by follicular (30.15%), and medullary (11.03%). In addition, 11 cases of anaplastic carcinoma, 2 cases of oncocytic carcinoma, and 2 cases of poorly differentiated thyroid carcinoma were reported. The average age at diagnosis of cutaneous metastases was 63.13 years, and the average time interval between the diagnoses of primary thyroid carcinoma and cutaneous metastases was 48.27 months. The most common location of metastases was the scalp (n = 48). Other common locations included the neck, chest, and face. The OS after diagnosis of metastases was only available in 34 patients with an average of 13.07 months. Of these 34 cases, 10 were medullary, 10 were papillary, 9 were anaplastic, and 5 had follicular carcinoma. This study represents an up-to-date review of the cases of thyroid carcinoma with cutaneous metastases. While cutaneous metastasis remains a rare finding, one needs a high index of suspicion, and their presence portends a poor prognosis.
PubMed: 38486397
DOI: 10.1177/01455613241239533 -
Frontiers in Oncology 2024Metastatic lung neuroendocrine carcinomas provide diagnostic challenges in identifying the cell of origin. High level calcitonin expression is not pathognomonic for...
Metastatic lung neuroendocrine carcinomas provide diagnostic challenges in identifying the cell of origin. High level calcitonin expression is not pathognomonic for medullary thyroid cancer. Tumor mutation analysis may provide essential clues regarding tissue origin and treatment targets. Oncogenic RET gene fusions have been identified in non-small cell lung cancer and non-medullary thyroid cancers, whereas RET point mutations are the key genetic finding in both inherited and sporadic MTC. Patients who receive radiation for the treatment of other cancers have an increased risk of developing a second malignancy, including a neuroendocrine carcinoma. Herein, we present a case of calcitonin-rich neuroendocrine carcinoma emerging on a background of prior radiation and chemotherapy for the treatment of Hodgkin's disease. Identification of a RET gene rearrangement (KIF5B-RET) led to initial successful treatment with selpercatinib, with eventual resistance associated with an activating mutation involving the MEK1 protein (MAP2K1 p. E102-I103 del) that led to relapse and progression of the disease.
PubMed: 38469239
DOI: 10.3389/fonc.2024.1360492 -
NPJ Precision Oncology Mar 2024Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative...
Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with an acquired EML4::ALK fusion. Combination of selpercatinib with the dual NTRK/ALK inhibitor entrectinib reduced the tumor burden, which was followed by appearance of NTRK3 solvent-front G623R mutation. Preclinical experiments validated selpercatinib plus larotrectinib or entrectinib inhibited RET/NTRK3 dependent cells, whereas selpercatinib plus entrectinib was necessary to inhibit cells with RET/NTRK3/ALK triple alterations or a mixture of cell population carrying these genetic alterations. Thus, RET-altered MTC adapted to selpercatinib and larotrectinib with acquisition of ETV6::NTRK3 and EML4::ALK oncogenes can be managed by combination of selpercatinib and entrectinib providing proof-of-concept of urgency of incorporating molecular profiling in real-time and personalized N-of-1 care transcending one-size-fits-all approach.
PubMed: 38438731
DOI: 10.1038/s41698-024-00563-4