CCNA2 and KIF23 are molecular targets for the prognosis of adenoid cystic carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumor type derived from glands. However, relationship between CCNA2 and KIF23, and adenoid cystic carcinoma remains unclear. METHODS: GSE36820 and GSE88804 profiles for ACC were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, the construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed. A gene expression heat map was generated to visually depict the expression difference of core genes between adenoid cystic carcinoma and normal samples. TargetScan was employed to identify miRNAs that regulated central DEGs. Western blotting (WB) was conducted for cell verification. RESULTS: A total of 885 DEGs were identified. GO and KEGG analyses revealed their main enrichment in responses to chemical stimuli, cell proliferation, tissue development, and regulation of cell proliferation. The GO and KEGG results indicated significant enrichment in aldosterone-regulated sodium reabsorption, the cell cycle, and the PPAR signaling pathway. Notably, core genes (CCNA2 and KIF23) were found to be highly expressed in Adenoid Cystic Carcinoma samples and expressed at low levels in normal samples. WB validated the overexpression of CCNA2 and KIF23 in the Adenoid Cystic Carcinoma group, confirming the protein-level changes associated with cell cycle, metastasis, apoptosis, and inflammatory factors in Adenoid Cystic Carcinoma groups with gene overexpression and knockout. CONCLUSIONS: CCNA2 and KIF23 exhibit high expression levels in ACC, suggesting their potential role as molecular targets for this malignancy.

A population study comparing tracheal and lung adenoid cystic carcinoma.

BACKGROUND: Thoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood. METHODS: Patients were identified from a Chinese cancer center (FUSCC) (2005-2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed. RESULTS: Totally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy. CONCLUSIONS: LACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.

Renal Metastasis Arising From a Pulmonary Adenoid Cystic Carcinoma: A Rare Case Report and Literature Review.

Adenoid cystic carcinoma (ACC), a rare malignancy, typically originates in salivary glands and is rarely found in other locations. In this case report, we describe a 54-year-old male patient who was presented to the Urology Department of Yantai Yuhuangding hospital with right-sided waist pain. The patient underwent percutaneous ultrasound-guided biopsies of lesions in the kidney and lung, which were histologically confirmed as primary adenoid cystic carcinoma of the lung and metastatic renal adenoid cystic carcinoma, respectively. Given the presence of multiple metastases, the patient received systemic palliative chemotherapy, which was well-tolerated and effectively controlled the tumor. At the last follow-up, there was no evidence of tumor progression in the patient.

Platinum-based adjuvant chemoradiotherapy versus adjuvant radiotherapy in patients with head and neck adenoid cystic carcinoma.

PURPOSE: The objective of the study was to assess the effectiveness and toxicity of platinum-based adjuvant chemoradiotherapy (POCRT) in comparison to postoperative radiotherapy (PORT) in patients with head and neck adenoid cystic carcinoma (HNACC). MATERIALS AND METHODS: This retrospective study analyzed patients diagnosed with HNACC at our center between January 2010 and April 2020. A 1:1 propensity score matching method was used to create a matched cohort. RESULTS: In this study, 206 patients were analyzed, with 147 patients (71.4%) receiving postoperative radiotherapy (PORT) and 59 patients (28.6%) receiving POCRT. Twenty-one patients experienced local-regional failure. The 3-, 5-, and 10-yr local-regional control (LRC) rate for the cohort were 92.0%, 90.6%, and 86.9%, respectively. In both the entire cohort and the matched cohort, the POCRT group exhibited superior LRC compared to the PORT group (Gray's test, all P < 0.05*). Multivariate analysis identified adjuvant concurrent chemotherapy as an independent prognostic factor for LRC (Competing risks regression, HR = 0.144, 95% CI 0.026-0.802, P = 0.027*). In addition, the POCRT group had higher incidences of upper gastrointestinal toxicity and hematologic toxicities, including leukopenia, neutropenia, and anemia (all P < 0.05*). CONCLUSION: In terms of reducing locoregional failures in HNACC patients, POCRT may potentially offer a more effective therapeutic approach than using PORT alone, although it also entails an augmented burden of treatment-related toxicity.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Adenoid Cystic Carcinoma of the Vulva: A Case Report.

Adenoid cystic carcinoma (ACC) of the vulva represents a highly uncommon type of female malignancy. Due to the absence of specific treatment guidelines, such cases are typically managed by the treatment protocols for vulvar cancer. Here, we report the case of a 52-year-old woman who presented with a painful right vulvar mass, leading to a diagnosis of ACC of the vulva after biopsy and immunohistochemical analysis. She underwent vulvectomy, bilateral inguinal lymphadenectomy, and targeted radiotherapy, and no evidence of recurrence has been found for three years, with ongoing monitoring for post-radiation effects. This case adds valuable insights into the management of ACC of the vulva and underscores the need for further research and guideline development to optimize care for future patients.

High-grade transformation in adenoid cystic carcinoma: Can it be diagnosed on cytology? A cytohistological correlation.

Adenoid cystic carcinomas (ADCC) are distinctive salivary gland neoplasms with characteristic histomorphology. The diagnosis of dedifferentiation/high-grade transformation (HGT) indicates poor prognosis and is most often made on histopathology. We present a case of ADCC arising from a minor salivary gland tumor exhibiting HGT, reaching up to the submandibular gland and having lymph node metastases, suspected on fine-needle aspiration cytology. The index case highlights the awareness of the entity of the HGT of salivary gland tumors and raises suspicion for cytological diagnosis.

High-grade salivary carcinomas: A current insight on diagnostic pathology and the key to clinical decision making.

High-grade carcinomas of the salivary glands are a group of several tumor entities with highly malignant histologic appearances, and have an aggressive biological behavior accompanied by poor a prognosis. In general, they require more intensive treatment than low- or intermediate-grade carcinomas. High-grade salivary carcinomas are rare and the microscopic features often overlap between different tumor types, making an appropriate diagnosis challenging in daily practice settings. However, with recent rapid advances in molecular pathology and molecular-targeted therapy in this field, there is a growing need to properly classify tumors, rather than just diagnosing the cases as "high-grade carcinomas". This leads to specific treatment strategies. In this article, we review representative high-grade salivary gland carcinomas, including salivary duct carcinoma and its histologic subtypes, high-grade mucoepidermoid carcinoma, solid-type adenoid cystic carcinoma, and high-grade transformation of low- or intermediate-grade carcinomas, and discuss their differential diagnoses and clinical implications. Other rare entities, such as neuroendocrine carcinoma, NUT carcinoma, and metastatic carcinoma, should also be considered before diagnosing high-grade carcinoma, NOS. Of these tumors, salivary duct carcinoma has received the most attention because of its strong association with androgen deprivation and anti-HER2 therapies. Other tumor-type-specific treatments include anti-TRK therapy for high-grade transformation of secretory carcinoma, but further therapeutic options are expected to be developed in the future. It should be emphasized that detailed histological evaluation with adequate sampling, in addition to the effective use of molecular ancillary tests, is of the utmost importance for a suitable diagnosis.

Molecular Aspects of Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma of the Salivary Gland.

BACKGROUND: Salivary gland tumors (SGTs) are rare and highly heterogeneous lesions, making diagnosis a challenging activity. In addition, the small number of studies and samples evaluated difficults the determination of prognosis and diagnosis. Despite the solid advances achieved by research, there is still an intense need to investigate biomarkers for diagnosis, prognosis and that explain the evolution and progression of SGTs. METHODS: We performed a comprehensive literature review of the molecular alterations focusing on the most frequent malignant SGTs: mucoepidermoid carcinoma and adenoid cystic carcinoma. RESULTS: Due to the importance of biomarkers in the tumorigenenic process, this review aimed to address the mechanisms involved and to describe molecular and biomarker pathways to better understand some aspects of the pathophysiology of salivary gland tumorigenesis. CONCLUSIONS: Molecular analysis is essential not only to improve the diagnosis and prognosis of the tumors but also to identify novel driver pathways in the precision medicine scenario.

Endotracheal enucleation and para-toluenesulfonamide injection for adenoid cystic carcinoma in the upper trachea: A novel therapeutic approach.

We present a case of an adenoid cystic carcinoma (ACC) located in the upper trachea, which resulted in significant airway blockage, that was unsuitable for surgical removal due to concerns about functional impairment. Instead, endotracheal enucleation via rigid bronchoscopy was performed initially, followed by the injection of a novel tumor ablation agent known as para-toluenesulfonamide (PTS). We detail the dosing regimen, effectiveness evaluation, and post-treatment follow-up. The study highlights the potential of PTS injection as a viable alternative treatment option for patients with ACC who cannot undergo surgical resection and feasibility of lipiodol to monitor treatment effect. This research adds to the existing knowledge on ACC treatment and provides new therapeutic possibilities for patients with tracheal ACC.

Unraveling the Molecular Complexity of Adenoid Cystic Carcinoma (ACC): A Comprehensive Exploration of Hub Genes, Protein-Protein Interaction (PPI) Networks, microRNA (miRNA) Involvement, and Drug-Gene Interactions (DGIs).

Background Adenoid cystic carcinoma (ACC) poses clinical challenges with its unique histology and potential for perineural invasion, recurrence, and distant metastases. Recent genomic advancements have unveiled key genetic alterations in ACC, offering insights into its pathogenesis. Aim This study aims to unravel the intricate molecular landscape of ACC through a comprehensive analysis of gene expression patterns. By integrating data from multiple microarray datasets, the study explores differentially expressed genes (DEGs), their functional enrichment, protein-protein interactions (PPI), hub genes, microRNA (miRNA) involvement, transcription factors, and potential drug-gene interactions. Methods Three microarray datasets (GSE88804, GSE153002, and GSE36820) related to ACC were selected from the Gene Expression Omnibus (GEO) repository. DEGs were identified using GEO2R and further analyzed for commonalities and differences. Functional enrichment analysis, including Gene Set Enrichment Analysis (GSEA), provided insights into biological processes, cellular components, molecular functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with ACC. PPI networks and hub genes were identified using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) (STRING Consortium, Lausanne, Switzerland) database and Cytoscape (Cytoscape Consortium, California, United States). The study also explored miRNAs, transcription factors, and potential drug-gene interactions. Results The integrated analysis revealed 339 common upregulated and 643 downregulated DEGs in ACC. Functional and pathway enrichment analyses unveiled the involvement of these genes in critical cellular processes, signaling cascades, and pathways. The PPI network, comprising 904 nodes and 4139 edges, highlighted the complexity of interactions. Hub genes, including KIF11, BUB1, and DLGAP5, were identified, shedding light on their pivotal roles in cell cycle regulation. The study also identified miRNAs (e.g., hsa-mir-7-5p and hsa-mir-138-5p) and transcription factors (e.g., E2F1 and TP53) associated with ACC. Drug-gene interactions have identified potential therapeutic options, including amsacrine and rucaparib. Conclusions The ACC gene expression highlights a nuanced molecular landscape, identifying pivotal hub genes such as KIF11 and CDK1 as potential therapeutic targets for ACC, given their roles in cell cycle progression. The dysregulation of microRNAs and transcription factors adds complexity to ACC's molecular profile. Exploration of drug-gene interactions reveals promising therapeutic strategies, involving FDA-approved drugs such as amsacrine and rucaparib, providing avenues for personalized interventions.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

Objective: The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods: The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results: Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Conclusion: Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level of Evidence: Level 3 (Prognosis - Cohort study).

The Fundamental Role of Multidisciplinary Approach in Complex Head and Neck Pathology: A Case Report of Maxillary Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare tumor, with a documented annual incidence ranging from 3 to 4.5 cases per million. It constitutes approximately 1% of all head and neck malignancies and around 10% of salivary gland tumors. It is imperative to adopt a multidisciplinary approach to ensure the most appropriate therapeutic outcome. Treatment strategies usually involve a multidisciplinary approach and may include surgery, radiotherapy, chemotherapy, or various combinations of these. In this context, we present a clinical case of ACC originating in the palate of a woman. Throughout this article, we will detail the diagnostic challenges and multidisciplinary treatment strategies implemented, emphasizing the importance of a comprehensive approach in cases of palatal ACC. In addition, we will discuss the rehabilitation process and the outcomes observed during the follow-up of this case.

Adenoid Cystic Carcinoma, Clinical Presentation, Current Treatment and Approaches Towards Novel Therapies.

Adenoid cystic carcinoma (AdCC) is a rare cancer originating from secretory glands with unknown aetiology. It is one of the most dominant malignant salivary tumours (MST). However, it can arise in other areas of the head and neck region and in secretory glands outside this area. It occurs at all ages, but is more frequent between 50-70 years of age and more common in females than in males. The symptoms of AdCC are generally unspecific and the clinical diagnosis of AdCC maybe challenging, partially due to its heterogenous histopathology and indolent growth. Moreover, there is a lack of good prognostic markers, and due to its rarity, it is difficult to predict which therapeutic methods are the most optimal for each patient, especially since very late recurrences occur. This review presents some major characteristics of AdCC and some current treatments for this disease.

Salivary gland-type cancers: cross-organ demographics of a rare cancer.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Transcription Factor MYB as Therapeutic Target: Current Developments.

The MYB protein is a pivotal player in the cellular transcriptional network, influencing major important processes such as cell proliferation, differentiation, and apoptosis. Because of its role in oncogenesis, MYB is now a compelling target for therapeutic interventions in cancer research. This review summarizes its molecular functions and current therapeutic approaches aiming to inhibit its oncogenic activity.

MYB alternative promoter activity is increased in adenoid cystic carcinoma metastases and is associated with a specific gene expression signature.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a head and neck cancer with a poor long-term prognosis that shows frequent local recurrences and distant metastases. The tumors are characterized by MYB oncogene activation and are notoriously unresponsive to systemic therapies. The biological underpinnings behind therapy resistance of disseminated ACC are largely unknown. Here, we have studied the molecular and clinical significance of MYB alternative promoter (TSS2) usage in ACC metastases. MATERIALS AND METHODS: MYB TSS2 activity was investigated in primary tumors and metastases from 26 ACC patients using RNA-sequencing and quantitative real-time PCR analysis. Differences in global gene expression between MYB TSS2 high and low cases were studied, and pathway analyses were performed. RESULTS: MYB TSS2 activity was significantly higher in ACC metastases than in primary tumors (median activity 15.1 vs 3.0, P = 0.0003). MYB TSS2 high ACC metastases showed a specific gene expression signature, including increased expression of multi-drug resistance genes and canonical MYB target genes, and suppression of the p53 and NOTCH pathways. CONCLUSIONS: Collectively, our findings indicate that elevated MYB TSS2 activity is associated with metastases, potential drug resistance, and augmented MYB-driven gene expression in ACC. Our study advocates the need for new therapies that specifically target MYB and drug resistance mechanisms in disseminated ACC.

Adenoid cystic carcinoma of the retromolar pad region: A case report.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignancies, mostly occurs in the major and minor salivary glands in the oral and maxillofacial region. The development of ACC in the retromolar pad is extremely rare, which limits establishing proper diagnosis and management. PRESENTATION OF CASE: A patient described a 2-month history of finding a mass behind the lower left posterior teeth. Based on the physical examination and radiographic findings, we got an initial impression of a benign mucocele, the nature of which was to be investigated further. Pathological examination of the resected tissue resulted in a diagnosis of ACC. Follow-up visits showed no recurrence during the subsequent 54 months. DISCUSSION: In cases with an uncertain diagnosis based on medical history, clinical features and imaging examinations, it is important to proceed carefully with the possibility of a tumor in mind. CONCLUSION: ACC in the retromolar pad is rare and can be easily misdiagnosed. Clinical, radiographic, and pathological evidence confirm a definitive diagnosis. Long-term follow-up is important for the full analysis of ACC treatment.

Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness.

Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC). SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.