Prognostic Relevance of Thyroid-Hormone-Associated Proteins in Adenoid Cystic Carcinoma of the Head and Neck.
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SUBMITTER: Schnoell J
PROVIDER: S-EPMC8703850 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Prognostic Relevance of Thyroid-Hormone-Associated Proteins in Adenoid Cystic Carcinoma of the Head and Neck.
Schnoell Julia J Kotowski Ulana U Jank Bernhard J BJ Stoiber Stefan S Gurnhofer Elisabeth E Schlederer Michaela M Heiduschka Gregor G Kenner Lukas L Kadletz-Wanke Lorenz L
Journal of personalized medicine 20211212 12
The proteins sodium iodide symporter (NIS), μ-crystallin (CRYM), and thyroid hormone receptor beta (THRB) have been associated with prognosis in various cancer entities. While NIS and THRB may serve as possible therapeutic targets, the role of CRYM in cancer is still unclear. Protein levels of 44 patients with adenoid cystic carcinoma of the head and neck were analyzed using immunohistochemistry and correlated with clinicopathological data and outcome. NIS was positive in 72%, CRYM was positive ...[more]
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Project description:Background/objectivesAdenoid Cystic Carcinoma (AdCC) is a rare malignant salivary gland tumor, with high rates of recurrence and distant metastasis. This study aims to stratify patients Relapse-Free Survival (RFS) using a combined model of clinical and radiomic features from preoperative MRI.MethodsThis retrospective study included patients with primary AdCC who underwent surgery and adjuvant radiotherapy. Segmentations were manually performed by two head and neck radiologists. Radiomic features were extracted using the 3D Slicer software. Descriptive statistics was performed. A Survival Random Forest model was employed to select which radiological feature predict RFS. Cox proportional hazards models were constructed using clinical, radiological variables or both. Synthetic data augmentation was applied to address the small sample size and improve model robustness. Models were validated on real data and compared using the C-index and Prediction Error Curves (PEC).ResultsThree Cox models were developed: one with clinical features (C-index = 0.67), one with radiomic features (C-index = 0.68), and one combining both (C-index = 0.77). The combined clinical-radiomic model had the highest predictive accuracy and outperformed models based on clinical or radiomic features. The combined model also exhibited the lowest mean Brier score in PEC analysis, indicating better predictive performance.ConclusionsThis study demonstrate that a combined radiomic-clinical model can predict RFS in AdCC patients. This model may provide clinicians a valuable tool in patient's management and may aid in personalized treatment planning.
| S-EPMC11640122 | biostudies-literature
Project description:ObjectivesSalivary gland adenoid cystic carcinoma (ACC) is rare, aggressive, and challenging to treat. Many ACCs have a t(6;9) chromosomal translocation resulting in a MYB-NFIB fusion gene, but the clinical significance is unclear. The purposes of this study were to describe the clinicopathologic factors impacting survival and to determine the prevalence and clinical significance of MYB-NFIB fusion.Study designCase series.MethodsMedical records of patients treated for ACC of the head and neck from 1974 to 2011 were reviewed and clinicopathologic data recorded. Fluorescence in situ hybridization (FISH) was used to detect MYB rearrangement in archival tumor tissue as a marker of MYB-NFIB fusion.ResultsOne hundred fifty-eight patients were included, with median follow-up 75.1 months. Median overall survival was 171.5 months (95% confidence interval [CI] = 131.9-191.6), and median disease-free survival was 112.0 months (95% CI = 88.7-180.4). Advanced stage was associated with decreased overall survival (adjusted ptrend < 0.001), and positive margins were associated with decreased disease-free survival (adjusted hazard ratio [aHR] = 8.80, 95% CI = 1.25-62.12, P = 0.029). Ninety-one tumors were evaluable using FISH, and 59 (65%) had evidence of a MYB-NFIB fusion. MYB-NFIB positive tumors were more likely than MYB-NFIB negative tumors to originate in minor salivary glands (adjusted prevalence ratios = 1.51, 95% CI = 1.07-2.12, P = 0.019). MYB-NFIB tumor status was not significantly associated with disease-free or overall survival (hazard ratio [HR] = 1.53, 95% CI = 0.77-3.02, P = 0.22 and HR = 0.91, 95% CI = 0.46-1.83, P = 0.80, respectively, for MYB-NFIB positive compared with MYB-NFIB negative tumors).ConclusionStage and margin status were important prognostic factors for ACC. Tumors with evidence of MYB-NFIB fusion were more likely to originate in minor salivary glands, but MYB-NFIB tumor status was not significantly associated with prognosis.Level of evidence4.
| S-EPMC4546892 | biostudies-literature
Project description:BackgroundThere is little evidence exploring prognostic effects of surgery and radiotherapy on adenoid cystic carcinoma (ACC) of the head and neck. This study sought to evaluate the prognostic effects of surgery or radiotherapy on ACC of the salivary gland, oropharynx, and nose, nasal cavity, and middle ear.MethodsIn this cohort study, the data of 2,392 participants with ACC of the head and neck were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Participants were divided into the salivary gland group (n=1,351), the mouth and oropharynx group (n=563), and the nose, nasal cavity, and middle ear group (n=478). Baseline characteristics were assessed via questionnaires or laboratory analysis and outcome variables were all-cause death and cancer-specific death of patients. Baseline data were collected in 2004, and patients were followed-up to 2016. The survival time of patients were recorded. Univariate and multivariate Cox regression analyses explored the effects of surgery and radiotherapy on overall prognosis of ACC patients. Fine-Gray test assessed the effects of surgery and radiotherapy on cancer-specific mortality of ACC patients.ResultsIn total, 766 died and 1,626 survived with a median survival time of 9.92 years. After adjusting for confounders, patients with ACC of the salivary gland who underwent surgery had a decreased risk of all-cause mortality [hazard ratio (HR) =0.51; 95% confidence interval (CI): 0.36-0.71] and cancer-specific mortality (HR =0.57; 95% CI: 0.34-0.97). Surgery was found to be a protective factor for the risk of all-cause mortality (HR =0.47; 95% CI: 0.28-0.78) and cancer-specific mortality (HR =0.70; 95% CI: 0.33-1.50) of patients with ACC of the mouth and oropharynx after adjusting for confounders. After adjusting for confounders, patients with ACC of the nose, nasal cavity, and middle ear who underwent surgery had a decreased risk of all-cause mortality (HR =0.46; 95% CI: 0.30-0.70) and cancer-specific mortality (HR =0.35; 95% CI: 0.20-0.61).ConclusionsSurgery was associated with a decreased risk of mortality in patients with ACC of the salivary gland, oropharynx, and nose, nasal cavity, and middle ear, which suggested the value of surgery for improving their prognosis.
| S-EPMC9742048 | biostudies-literature
Project description:BackgroundAdenoid cystic carcinoma of head and neck (ACCHN) is an uncommon head and neck cancers, whose predilection age is 40 to 60. Some studies have revealed that early-onset cancers, such as colorectal cancers and esophageal adenocarcinoma, might present some unique clinicopathological features and have different prognosis with late-onset ones. However, little is known about the early-onset ACCHN. This study aimed to develop a prognostic nomogram for overall survival (OS) of patients younger than 40 with ACCHN.MethodsCases with ACCHN from 1975 to 2016 were retrieved from SEER-18 program. Demographic, clinical, and survival outcomes data of patients were identified for further analysis. The caret package was used to randomly divide early-onset patients into a training cohort and a validation cohort. A prognostic nomogram was constructed based on the univariate and multivariate Cox analysis. The discriminative ability and calibration power of the nomogram was evaluated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve.ResultsA total of 5858 cases with ACCHN were selectively retrieved from SEER program in this study. The number of patients younger than 40, which was defined as early-onset ACCHN in this study, was 825. Based on the outcomes of multivariate analysis, tumor size, chemotherapy, surgery, and stage were selected for the construction of nomogram to predict 10-year OS. The C-index was 0.792 (95%CI 0.760-0.823) and 0.776 (95%CI 0.720-0.832) in the training and validation set, respectively. The area under the ROC curve values were 0.875 (95%CI 0.810-0.940) and 0.833(95%CI 0.754-0.912). The calibration plot indicated that this nomogram had proper calibration in both the training and validation cohorts.ConclusionA novel prognostic nomogram for early-onset ACCHN was constructed and validated in this study. This nomogram could be applied for assisting clinicians to more accurately assess the prognosis of young patients, which might facilitate clinical decision-making and subsequent follow-up.
| S-EPMC10126692 | biostudies-literature
Project description:PurposeAlthough postoperative radiotherapy (PORT) is demonstrably effective in local control of head and neck adenoid cystic carcinoma (HNACC), its application is controversial and the subset of patients who would benefit most from PORT is unknown. Herein, we analyzed the data of HNACC patients to clarify the role of PORT.MethodsWe retrospectively reviewed 187 patients with nonmetastatic HNACC who underwent surgical resection between 2005 and 2019. The study endpoints were locoregional failure-free survival (LRFFS), progression-free survival (PFS), and overall survival (OS). Subgroup analysis and recursive partitioning analysis (RPA) were performed to identify patients most likely to benefit from PORT.ResultsWith a median follow-up of 84.7 months, the 5-year LRFFS, PFS, and OS were 70.0%, 52.6%, and 86.4%, respectively. Survival was significantly shorter in patients who experienced local failure than in those who did not (5-year OS: 88.1% vs. 80.5%, P = 0.001). The local failure rate was significantly lower in patients who underwent PORT (16.9% vs. 31.0%, P = 0.021), despite the high frequency of adverse factors. Especially, significant decreases in local failure and similar OS rates could be obtained after PORT among patients with positive margins, T2-4 stage disease, and minor salivary gland tumors. The RPA model for PFS categorized patients into four groups according to three prognostic factors (T-stage, location, and sex). The RPA model for LRFFS and OS suggested three groups based on two factors (T-stage, margin for LRFFS; T-stage, grade 3 for OS).ConclusionPORT could prevent dismal survival, while significantly reducing local failures in high-risk HNACC patients.
| S-EPMC9716721 | biostudies-literature
Project description:Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11-0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12-0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.
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Project description:Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC. In several solid tumors, tertiary lymphoid structures (TLS) are associated with improved survival. This study aims to investigate the role of distribution patterns of tumor infiltrating immune cells (TIL) in ACC. A cohort of 50 patients from three different cancer centers was available for analysis. Sections were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to their distribution of TIL. Patterns were determined as infiltrated-excluded, infiltrated-inflamed and presence of tertiary lymphoid structures. About half of the cases showed an infiltrated-excluded TIL pattern and only a minority of six cases had TLS present within the tumor. Within the inflamed phenotype CD3+ cells were by far the most abundant lymphocyte subtype, and within this compartment, CD8+ T cells were predominant. There was no influence on overall or disease-free survival by any of the TIL patterns. This indicates that ACC is a tumor with very low immunogenicity and even abundance of lymphocytes does not seem to improve prognosis for this disease. Therefore, the observed lack of response towards immunotherapy is not surprising and other methods to induce recognition of ACC by the immune system must be found.
| S-EPMC8946094 | biostudies-literature
Project description:IntroductionAdenoid cystic carcinoma (AdCC) is a rare tumour as it accounts for about 10% of all salivary gland neoplasms. It occurs in all age groups with a predominance of women, but no risk factors have been identified to date. Although AdCC behaves as a slow-growing tumour, it is characterized by multiple and late recurrences. Therefore, we aim to update the knowledge of the treatment options in advanced and recurrent cases.Materials and methodsWe performed a systematic literature review to provide a synthesis of the practical knowledge required for AdCC non-surgical management. Altogether, 99 out of the 1208 available publications were selected for analysis.ResultsAdCC is described as a basaloid tumour consisting of epithelial and myoepithelial cells. Immunohistochemistry is useful for diagnosis (PS100, Vimentin, CD117, CKit, muscle actin, p63) and for prognosis (Ki67). Identified mutations could lead to therapeutic opportunities (MYB-NFIB, Notch 1). The work-up is mainly based on neck and chest CT scan and MRI, and PET-CT with 18-FDG or PSMA can be considered. Surgical treatment remains the gold standard in resectable cases. Post-operative intensity modulated radiotherapy is the standard of care, but hadron therapy may be used in specific situations. Based on the available literature, no standard chemotherapy regimen can be recommended.ConclusionThere is currently no consensus on the use of chemotherapy in AdCC, either concomitantly to RT in a postoperative setting or at a metastatic stage. Further, the available targeted therapies do not yet provide significant tumour response.
| S-EPMC9176735 | biostudies-literature
Project description:BackgroundTreatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck.MethodsOne hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis.ResultsPSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p = .04).ConclusionsPSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.
| S-EPMC7275445 | biostudies-literature
Project description:BackgroundDespite Adenoid cystic carcinoma (ACC) with cribriform or tubular components being recognized as a potentially indolent malignancy, ACC displaying solid or, more rarely, high-grade transformation (HGT) components is considered a more aggressive variant of the disease. As it is difficult to measure the proportion of the solid component objectively, and the role of HGT in the current grading system remains unclear, the prognostic influence of tumor grading remains controversial. In addition, postoperative radiotherapy (PORT) has been proven to be effective in local control of ACC of the head and neck (ACCHN) with a high rate of nerve invasion and close surgical margin. However it remains to be explored that whether PORT could improve the survival of patients with ACC, particularly those with HGT.MethodsA series of 73 surgically treated primary ACCHN cases were retrospectively accessed. Immunohistochemical staining was performed to observe the biphasic ductal-myoepithelial differentiation and to identify the HGT components of ACC for tumor grading. The correlation between tumor grading and clinicopathological characteristics was analyzed. Univariate and multivariate prognostic analysis were performed for progression-free survival (PFS) and overall survival (OS).ResultsOf the 73 included cases, 47 were grade I-II ACC and 26 were grade III ACC. Among the grade III cases, 14 with loss of biphasic ductal-myoepithelial differentiation identified by immunostaining were classified as HGT, and could be distinguished from conventional grade III cases. These HGT cases were correlated with a high propensity of lymph node metastases and more advanced stage. Univariate analysis demonstrated that tumor grading, perineural invasion, T stage, stage groups, and PORT were predictors for PFS, whereas tumor grading, margin status, and PORT were predictors for OS. However, only tumor grading and PORT were independent predictors for PFS and OS. The patients with HGT had significantly worse prognosis than those with conventional ACC. Moreover, disease progression tended to occur more frequently in younger patients. Among the patients with HGT, those who received PORT had a longer median survival time than those who did not.ConclusionHGT ACC identified by loss of biphasic differentiation should be considered in tumor grading. Tumor grading and PORT were independent predictors for disease progression and OS in surgically treated ACCHN patients.
| S-EPMC8063729 | biostudies-literature