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13 pages, 1697 KiB  
Article
Correlation Between MRI Characteristic of Osteosarcoma with 2-Year Survival Outcomes
by Mohd Noor Akmal Adam, Emilia Rosniza Mohammed Rusli, Erica Yee Hing, Juliana Fairuz Maktar, Ckhai Loh, Nor Hazla Mohamed Haflah and Faizah Mohd Zaki
Diagnostics 2025, 15(13), 1707; https://doi.org/10.3390/diagnostics15131707 - 3 Jul 2025
Viewed by 409
Abstract
Background: Magnetic resonance imaging (MRI) plays a crucial role in staging and preoperative evaluation in osteosarcoma patient. Fewer studies have focused on 2-year survival, which reflects tumour aggressiveness and early disease progression. This study examines the association between MRI characteristics and 2-year survival [...] Read more.
Background: Magnetic resonance imaging (MRI) plays a crucial role in staging and preoperative evaluation in osteosarcoma patient. Fewer studies have focused on 2-year survival, which reflects tumour aggressiveness and early disease progression. This study examines the association between MRI characteristics and 2-year survival outcomes in osteosarcoma to better understand the imaging characteristic of high-risk patients. Methods: A retrospective case–control study was conducted at a tertiary university hospital. Patients diagnosed with osteosarcoma between 2010 and 2022 were included if they had a pre-treatment MRI and at least 2 years of follow-up. MRI scans were reviewed by two blinded radiologists to assess tumour location, volume, growth pattern, presence of fluid–fluid levels (FFL), pathological fractures, skip metastases, neurovascular bundle involvement, regional lymphadenopathy, and physeal or joint involvement. Statistical analyses, including Fisher’s exact test, Chi-square test, and Mann–Whitney U test, were performed to determine associations between MRI features and survival outcomes. Results: Twenty-eight patients (n = 28) met the inclusion criteria. Larger tumour volume (>300 mls) was significantly associated with poorer 2-year survival (p = 0.008). The presence of skip metastases also correlated with worse outcomes (p = 0.041). While presence of FFL, concentric growth pattern, regional lymphadenopathy, and physeal involvement showed trends toward poorer prognosis, these associations were not statistically significant. Conclusions: MRI characteristics, particularly tumour volume and skip metastases, are significant prognostic indicators of 2-year survival in osteosarcoma. These findings highlight the potential role of MRI in risk stratification and treatment planning, aiding in the identification of high-risk patients that can help with management. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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7 pages, 686 KiB  
Case Report
Treatment of Leptomeningeal Disease with Tepotinib in a Patient with Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Presenting with Extensive Metastasis Involving Duodenum
by Jacquelyn Shugarts, Aida Amado, Taylor Praska, Monica Camou and Jiaxin Niu
Reports 2025, 8(2), 96; https://doi.org/10.3390/reports8020096 - 18 Jun 2025
Viewed by 508
Abstract
Background and Clinical Significance: The mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is a rare genetic alteration occurring in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) are the approved treatment for first-line therapy in a metastatic setting. However, the unusual [...] Read more.
Background and Clinical Significance: The mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is a rare genetic alteration occurring in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) are the approved treatment for first-line therapy in a metastatic setting. However, the unusual presentation of gastrointestinal metastasis and leptomeningeal carcinomatosis (LMD) poses significant treatment challenges. Case Presentation: Here we report a case of a 72-year-old male with metastatic METex14-positive NSCLC, presenting with brain and duodenal metastases. Conclusions: The patient responded exceptionally well to first-line chemoimmunotherapy, achieving clinically complete remission for 2 years. He subsequently developed cerebellar metastasis and leptomeningeal disease (LMD) but demonstrated a remarkable response to tepotinib and continued to enjoy radiographic complete remission over 2.5 years at the time of this report. Full article
(This article belongs to the Section Oncology)
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11 pages, 386 KiB  
Article
Predicting the Unexpected: Clinicopathological Insights into Skip Metastasis in Papillary Thyroid Carcinoma
by Ibrahim Burak Bahcecioglu, Adile Begum Bahcecioglu, Sevket Baris Morkavuk, Yasin Hatipoglu, Sumeyra Guler, Mujdat Turan, Gokhan Giray Akgul, Nese Ersoz Gulcelik and Mehmet Ali Gulcelik
J. Clin. Med. 2025, 14(12), 4255; https://doi.org/10.3390/jcm14124255 - 15 Jun 2025
Viewed by 432
Abstract
Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment [...] Read more.
Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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10 pages, 368 KiB  
Article
Non-Small Cell Lung Cancer Patients with Skip-N2 Metastases Have Similar Survival to N1 Patients—A Multicenter Analysis
by Georg Schlachtenberger, Simon Schallenberg, Fabian Doerr, Hruy Menghesha, Christopher Gaisendrees, Andres Amorin, Alberto Lopez-Pastorini, Reinhard Büettner, Alexander Quaas, David Horst, Frederick Klauschen, Nikolaj Frost, Jens C. Rueckert, Jens Neudecker, Khosro Hekmat and Matthias B. Heldwein
J. Pers. Med. 2025, 15(3), 113; https://doi.org/10.3390/jpm15030113 - 14 Mar 2025
Viewed by 736
Abstract
Introduction: Nodal involvement is one of the most important prognostic factors in NSCLC. Skip-N2 metastasis (N0N2), which is N2 metastasis in the absence of N1 metastasis, occurs in approximately 20–30% of patients. According to the International Association for the Study of Lung Cancer, [...] Read more.
Introduction: Nodal involvement is one of the most important prognostic factors in NSCLC. Skip-N2 metastasis (N0N2), which is N2 metastasis in the absence of N1 metastasis, occurs in approximately 20–30% of patients. According to the International Association for the Study of Lung Cancer, N1 and N0N2 patients may have comparable long-term survival, considering their similar tumor stages. However, this conclusion remains controversial. Therefore, we carried out this multicenter study to examine the long-term survival and disease-free interval (DFI) of N0N2- and N1 patients. Methods: One-, three-, and five-year survival rates were measured. Kaplan–Meier curves and a Cox proportional hazards model assessed survival and were used to identify prognostic factors for overall survival. Results: Between January 2010 and December 2020, 273 N0N2 and N1 patients were included in our analysis. Of those patients, 77 showed N0N2 and 196 N1. Baseline characteristics did not differ significantly between groups. Between N0N2 and N1 patients, there were no significant differences in one- (p = 0.67), three- (p = 0.20), and five-year (p = 0.27) survival. Furthermore, DFI did not differ between groups (p = 0.45). Conclusions: Our findings indicate that N0N2 patients have a prognosis comparable to that of patients with N1 disease. These results indicate that patients with N0N2 have a similar prognosis to N1 patients. N2-NSCLC is heterogeneous and would benefit from a more precise subdivision and differential treatment in the upcoming UICC 9 classification. The following question remains: are we overtreating N0N2 patients or undertreating N1 patients? Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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35 pages, 9144 KiB  
Review
Multimodal Imaging of Osteosarcoma: From First Diagnosis to Radiomics
by Maurizio Cè, Michaela Cellina, Thirapapha Ueanukul, Gianpaolo Carrafiello, Rawee Manatrakul, Phatthawit Tangkittithaworn, Suphaneewan Jaovisidha, Praman Fuangfa and Donald Resnick
Cancers 2025, 17(4), 599; https://doi.org/10.3390/cancers17040599 - 10 Feb 2025
Cited by 4 | Viewed by 5224
Abstract
Osteosarcoma is a primary malignant bone tumor characterized by the production of an osteoid matrix. Although histology remains the definitive diagnostic standard, imaging plays a crucial role in diagnosis, therapeutic planning, and follow-up. Conventional radiography serves as the initial checkpoint for detecting this [...] Read more.
Osteosarcoma is a primary malignant bone tumor characterized by the production of an osteoid matrix. Although histology remains the definitive diagnostic standard, imaging plays a crucial role in diagnosis, therapeutic planning, and follow-up. Conventional radiography serves as the initial checkpoint for detecting this pathology, which often presents diagnostic challenges due to vague and nonspecific symptoms, especially in its early stages. Today, the integration of different imaging techniques enables an increasingly personalized diagnosis and management, with each contributing unique and complementary information. Conventional radiography typically initiates the imaging assessment, and the Bone Reporting and Data System (Bone-RADS) of the Society of Skeletal Radiology (SSR) is a valuable tool for stratifying the risk of suspicious bone lesions. CT is the preferred modality for evaluating the bone matrix, while bone scans and PET/CT are effective for detecting distant metastases. MRI reveals the extent of the lesion in adjacent soft tissues, the medullary canal, and joints, as well as its relationship to neurovascular structures and the presence of skip lesions. Advanced techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), and perfusion MRI help characterize the tumor environment and assess treatment response. Osteosarcoma comprises a range of subtypes with differing clinical and imaging characteristics, some of which are particularly distinctive, such as in the case of telangiectatic osteosarcoma. Knowledge of these variants can guide radiologists in the differential diagnosis, which includes both central and surface forms, ranging from highly aggressive to more indolent types. In this review, we present a wide range of representative cases from our hospital case series to illustrate both typical and atypical imaging presentations. Finally, we discuss recent advancements and challenges in applying artificial intelligence approaches to the imaging of osteosarcoma. Full article
(This article belongs to the Special Issue Advances in Oncological Imaging)
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14 pages, 6435 KiB  
Article
The Importance of Suppressing Pathological Periostin Splicing Variants with Exon 17 in Both Stroma and Cancer
by Kana Shibata, Nobutaka Koibuchi, Fumihiro Sanada, Naruto Katsuragi, Yuko Kanemoto, Yasuo Tsunetoshi, Shoji Ikebe, Koichi Yamamoto, Ryuichi Morishita, Kenzo Shimazu and Yoshiaki Taniyama
Cells 2024, 13(17), 1410; https://doi.org/10.3390/cells13171410 - 23 Aug 2024
Viewed by 1483
Abstract
Background: Periostin (POSTN) is a type of matrix protein that functions by binding to other matrix proteins, cell surface receptors, or other molecules, such as cytokines and proteases. POSTN has four major splicing variants (PN1–4), which are primarily expressed in fibroblasts and cancer. [...] Read more.
Background: Periostin (POSTN) is a type of matrix protein that functions by binding to other matrix proteins, cell surface receptors, or other molecules, such as cytokines and proteases. POSTN has four major splicing variants (PN1–4), which are primarily expressed in fibroblasts and cancer. We have reported that we should inhibit pathological POSTN (PN1–3), but not physiological POSTN (PN4). In particular, pathological POSTN with exon 17 is present in both stroma and cancer, but it is unclear whether the stroma or cancer pathological POSTN should be suppressed. Methods and Results: We transplanted 4T1 cells (breast cancer) secreting POSTN with exon 17 into 17KO mice lacking POSTN exon 17 to suppress stromal POSTN with exon 17. The results show that 17KO mice had smaller primary tumors and fewer metastases. Furthermore, to suppress cancer POSTN with exon 17, 4T1 cells transfected with POSTN exon 17 skipping oligo or control oligo were transplanted from the tail vein into the lungs. The results show that POSTN exon 17 skipping oligo significantly suppressed lung metastasis. Conclusions: These findings suggest that it is important to suppress POSTN exon 17 in both stroma and cancer. Antibody targeting POSTN exon 17 may be a therapeutic candidate for breast cancer. Full article
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8 pages, 944 KiB  
Article
Prognostic Value of Lymph Node Ratio (LNR) in Patients with Postoperative N2 Feature in Non-Small Cell Lung Cancer (NSCLC)
by Mariusz Piotr Łochowski, Justyna Chałubińska-Fendler, Aleksandra Szlachcińska, Barbara Łochowska, Daniel Brzeziński, Jacek Kaczmarski and Józef Kozak
J. Clin. Med. 2024, 13(15), 4570; https://doi.org/10.3390/jcm13154570 - 5 Aug 2024
Cited by 3 | Viewed by 1408
Abstract
Introduction: One of the most important prognostic factors in non-small cell lung cancer (NSCLC), a condition with a high mortality rate, is the presence of mediastinal lymph node metastases alongside distant metastases. The aim of this study was to evaluate the prognostic value [...] Read more.
Introduction: One of the most important prognostic factors in non-small cell lung cancer (NSCLC), a condition with a high mortality rate, is the presence of mediastinal lymph node metastases alongside distant metastases. The aim of this study was to evaluate the prognostic value of selected parameters of N2 stage NSCLC with a special focus on lymph node ratio (LNR). Material: The study included 163 patients (61 women and 102 men) operated on due to NSCLC, postoperatively diagnosed as stage N2. The age of the patients ranged from 38 to 82 years (mean age: 62.4 years). The effects of the following factors on clinical data and survival rate were assessed: N1 stage, total number of all metastatic nodes, LNR and LNR N2 ratios, and the presence of skip, single- or multistation metastases. Results: Univariate analysis showed patient survival to be correlated with LNR and LNR N2 ratios, single/multistation metastases, and the number of nodes involved in metastasis. A multivariate model based on patient clinical data found nicotine dependence (p = 0.013), LNR > 0.26 (p = 0.004), and Charlson Comorbidity Index (CCI) value > 3 (p = 0.014) to be independent adverse prognostic factors in this group. Conclusions: LNR ratio is a significant cancer disease-derived independent prognostic factor for patients with postoperative N2 stage NSCLC. In addition, smoking and comorbidities also appear to have prognostic value. Full article
(This article belongs to the Special Issue Non-small Cell Lung Cancer: Current Updates and Perspectives)
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12 pages, 1640 KiB  
Article
Adequacy of Disease Control by Supraomohyoid Neck Dissection in cT1/T2 Tongue Cancer
by Andrea Iandelli, Filippo Marchi, An-Chieh Chen, Chi-Kuan Young, Chun-Ta Liao, Chung-Kan Tsao, Chung-Jan Kang, Hung-Ming Wang, Tung-Chieh Joseph Chang and Shiang-Fu Huang
J. Pers. Med. 2022, 12(9), 1535; https://doi.org/10.3390/jpm12091535 - 19 Sep 2022
Cited by 6 | Viewed by 2575
Abstract
Background: Patients affected by oral tongue squamous cell carcinoma (OTSCC) underwent a supraomohyoid neck dissection (SOHND) or modified radical neck dissection (mRND) according to the clinical nodal status (cN0 vs. cN+). We investigate whether the type of neck dissection affects survival with the [...] Read more.
Background: Patients affected by oral tongue squamous cell carcinoma (OTSCC) underwent a supraomohyoid neck dissection (SOHND) or modified radical neck dissection (mRND) according to the clinical nodal status (cN0 vs. cN+). We investigate whether the type of neck dissection affects survival with the presence of extranodal extension (ENE) and multiple nodal metastases (MNM). Methods: We conducted a retrospective study enrolling surgically treated patients affected by cT1/T2 OTSCC and MNM or ENE. The outcomes assessed were: overall survival (OS), disease-free survival (DFS), and neck-control- and metastases-free survival (NC-MFS). Survival curves were plotted by the Kaplan–Meier method and the log-rank test. Furthermore, we conducted a multivariable analysis with the Cox regression model. Results: We included a total of 565 patients (36% cT1, 64% cT2). Of these, 501 patients underwent a SOHND, and 64 underwent an mRND. A total of 184 patients presented rpN+, with 28.7% of these in the SOHND group and 62.5% of these in the mRND group. We identified no significant differences in OS, DFS, and NC-MFS in the whole pN+ cohort, in the MNM, and the ENE subgroups. In the multivariable analysis, the type of ND did not affect OS and DFS. Conclusions: Treating cT1-2 N0/+ tongue cancer with SOHND is oncologically safe. ENE and MNM patients do not benefit from an mRND. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
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11 pages, 1223 KiB  
Article
Predictive Factors for Skip Lymph Node Metastasis and Their Implication on Recurrence in Papillary Thyroid Carcinoma
by Young-Jae Ryu, Seong-Young Kwon, Soo-Young Lim, Yong-Min Na and Min-Ho Park
Biomedicines 2022, 10(1), 179; https://doi.org/10.3390/biomedicines10010179 - 16 Jan 2022
Cited by 8 | Viewed by 2829
Abstract
Skip lymph node (LN) metastases in papillary thyroid carcinoma (PTC) belong to N1b classification in the absence of central neck LN involvement. This study aimed to evaluate the predictive factors of skip metastases and their impact on recurrence in PTC patients with pN1b. [...] Read more.
Skip lymph node (LN) metastases in papillary thyroid carcinoma (PTC) belong to N1b classification in the absence of central neck LN involvement. This study aimed to evaluate the predictive factors of skip metastases and their impact on recurrence in PTC patients with pN1b. A total of 334 PTC patients who underwent total thyroidectomy with LN dissection (central and lateral neck compartment) followed by radioactive iodine ablation were included. Patients with skip metastases tended to have a small primary tumor (≤1 cm) and single lateral neck level involvement. Tumor size ≤ 1 cm was an important predictive factor for skip metastases. Univariate analysis for recurrence showed that patients with a central LN ratio > 0.68, lateral LN ratio > 0.21, and stimulated thyroglobulin (Tg) levels > 7.3 ng/mL had shorter RFS (recurrence-free survival). The stimulated Tg level was associated with shorter RFS on multivariate analysis (>7.3 vs. ≤7.3 ng/mL; hazard ratio, 4.226; 95% confidence interval, 2.226−8.022; p < 0.001). Although patients with skip metastases tended to have a small primary tumor and lower burden of lateral neck LN involvement, there was no association between skip metastases and RFS in PTC with pN1b. Stimulated Tg level was a strong predictor of recurrence. Full article
(This article belongs to the Special Issue Recent Advances in Thyroid Cancer: From Diagnosis to Treatment)
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11 pages, 1410 KiB  
Article
Survival Analysis in Single N2 Station Lung Adenocarcinoma: The Prognostic Role of Involved Lymph Nodes and Adjuvant Therapy
by Marco Chiappetta, Filippo Lococo, Giovanni Leuzzi, Isabella Sperduti, Emilio Bria, Leonardo Petracca Ciavarella, Felice Mucilli, Pier Luigi Filosso, Giovannibattista Ratto, Lorenzo Spaggiari, Francesco Facciolo and Stefano Margaritora
Cancers 2021, 13(6), 1326; https://doi.org/10.3390/cancers13061326 - 16 Mar 2021
Cited by 8 | Viewed by 2550
Abstract
Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics [...] Read more.
Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. Results: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417–5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001–4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. Conclusions: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified. Full article
(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)
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11 pages, 992 KiB  
Article
Clinicopathologic and Imaging Features of Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations
by Subba R. Digumarthy, Dexter P. Mendoza, Eric W. Zhang, Jochen K. Lennerz and Rebecca S. Heist
Cancers 2019, 11(12), 2033; https://doi.org/10.3390/cancers11122033 - 17 Dec 2019
Cited by 29 | Viewed by 4189
Abstract
MET exon 14 (METex14) skipping mutations are an emerging potentially targetable oncogenic driver mutation in non-small-cell lung cancer (NSCLC). The imaging features and patterns of metastasis of NSCLC with primary METex14 skipping mutations (METex14-mutated NSCLC) are not well [...] Read more.
MET exon 14 (METex14) skipping mutations are an emerging potentially targetable oncogenic driver mutation in non-small-cell lung cancer (NSCLC). The imaging features and patterns of metastasis of NSCLC with primary METex14 skipping mutations (METex14-mutated NSCLC) are not well described. Our goal was to determine the clinicopathologic and imaging features that may suggest the presence of METex14 skipping mutations in NSCLC. This IRB-approved retrospective study included NSCLC patients with primary METex14 skipping mutations and pre-treatment imaging data between January 2013 and December 2018. The clinicopathologic characteristics were extracted from electronic medical records. The imaging features of the primary tumor and metastases were analyzed by two thoracic radiologists. In total, 84 patients with METex14-mutated NSCLC (mean age = 71.4 ± 10 years; F = 52, 61.9%, M = 32, 38.1%; smokers = 47, 56.0%, nonsmokers = 37, 44.0%) were included in the study. Most tumors were adenocarcinoma (72; 85.7%) and presented as masses (53/84; 63.1%) that were peripheral in location (62/84; 73.8%). More than one in five cancers were multifocal (19/84; 22.6%). Most patients with metastatic disease had only extrathoracic metastases (23/34; 67.6%). Fewer patients had both extrathoracic and intrathoracic metastases (10/34; 29.4%), and one patient had only intrathoracic metastases (1/34, 2.9%). The most common metastatic sites were the bones (14/34; 41.2%), the brain (7/34; 20.6%), and the adrenal glands (7/34; 20.6%). Four of the 34 patients (11.8%) had metastases only at a single site. METex14-mutated NSCLC has distinct clinicopathologic and radiologic features. Full article
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15 pages, 2187 KiB  
Article
The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies
by Nele Van Der Steen, Karen Zwaenepoel, Giulia Mazzaschi, Rosa A. Luirink, Daan P. Geerke, Ken Op de Beeck, Christophe Hermans, Marcello Tiseo, Paul Van Schil, Filip Lardon, Paul Germonpré, Christian Rolfo, Elisa Giovannetti, Godefridus J. Peters and Patrick Pauwels
Molecules 2019, 24(24), 4443; https://doi.org/10.3390/molecules24244443 - 4 Dec 2019
Cited by 5 | Viewed by 6018
Abstract
The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different [...] Read more.
The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different c-Met aberrations (overexpression, amplification and mutations) in 153 primary, therapy-naïve resection samples and their paired metastases, from Biobank@UZA. Furthermore, we determined the correlation of c-Met expression with clinicopathological factors, Epidermal Growth Factor Receptor (EGFR)-status and TP53 mutations. Our results showed that c-Met expression levels in primary tumors were comparable to their respective metastases. Five different mutations were detected by deep sequencing: three (E168D, S203T, N375S) previously described and two never reported (I333T, G783E). I333T, a new mutation in the Sema(phorin) domain of c-Met, might influence the binding of antibodies targeting the HGF-binding domain, potentially causing innate resistance. E168D and S203T mutations showed a trend towards a correlation with high c-Met expression (p = 0.058). We found a significant correlation between c-MET expression, EGFR expression (p = 0.010) and EGFR mutations (p = 0.013), as well as a trend (p = 0.057) with regards to TP53 mutant activity. In conclusion this study demonstrated a strong correlation between EGFR mutations, TP53 and c-Met expression in therapy-naïve primary resection samples. Moreover, we found two new c-Met mutations that warrant further studies. Full article
(This article belongs to the Special Issue Drug Resistance in Targeted Cancer Therapy)
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