Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck

Weert, Stijn van; Reinhard, Rinze; Bloemena, Elisabeth; Buter, Jan; Witte, Birgit I.; Vergeer, Marije R.; Leemans, C. René

doi:10.1002/hed.24613

Cited by 43 publications

(33 citation statements)

References 33 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generally, ACC is being portrayed as an indolent disease; however, it has become clear that this is not always the case . We fully acknowledge that the rarity and the small number of patients represent a significant limitation of our study.…”

Section: Discussionmentioning

confidence: 93%

“…The MYB‐NFIB fusion results in an increased expression of the protein Myb . Myb is important for the growth of multiple solid tumors, and MYB protein overexpression in ACC is associated with a more aggressive clinical course . For example, Mitani et al reported that the level of MYB expression in identical histological subtypes of ACC is associated with a shorter survival time.…”

Section: Discussionmentioning

confidence: 99%

“…However, the demand for larger cohorts and studies does not solve day-to-day clinical management questions: for example, how to identify the subset of patients with ACC with a more aggressive clinical course. Notably, despite various studies outlining the prognostic relevance of molecular markers [5,9,15,16,42,43,[48][49][50][51][52][53][54], clinical guidelines currently rely on staging, margin status [55], perineural invasion [56], and resectability for treatment stratification (NCCN guidelines Version 2/2018; www.nccn.org, last accessed 12/22/2018).…”

Section: Discussionmentioning

confidence: 99%

“…(C): Utility assessment of molecular findings is twofold: (a) identification of potential actionable alterations in patients with nonresectable tumors (see also Table 1) Integrated Molecular Diagnostics in ACC the protein Myb [43]. Myb is important for the growth of multiple solid tumors, and MYB protein overexpression in ACC is associated with a more aggressive clinical course [33,[47][48][49]. For example, Mitani et al [40] reported that the level of MYB expression in identical histological subtypes of ACC is associated with a shorter survival time.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Thierauf

Ramamurthy

et al. 2019

The Oncologist

View full text Add to dashboard Cite

Background Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy without effective systemic therapies. Delineation of molecular profiles in ACC has led to an increased number of biomarker‐stratified clinical trials; however, the clinical utility and U.S.‐centric financial sustainability of integrated next‐generation sequencing (NGS) in routine practice has, to our knowledge, not been assessed. Materials and Methods In our practice, NGS genotyping was implemented at the discretion of the primary clinician. We combined NGS‐based mutation and fusion detection, with MYB break‐apart fluorescent in situ hybridization (FISH) and MYB immunohistochemistry. Utility was defined as the fraction of patients with tumors harboring alterations that are potentially amenable to targeted therapies. Financial sustainability was assessed using the fraction of global reimbursement. Results Among 181 consecutive ACC cases (2011–2018), prospective genotyping was performed in 11% (n = 20/181; n = 8 nonresectable). Testing identified 5/20 (25%) NOTCH1 aberrations, 6/20 (30%) MYB‐NFIB fusions (all confirmed by FISH), and 2/20 (10%) MYBL1‐NFIB fusions. Overall, these three alterations (MYB/MYBL1/NOTCH1) made up 65% of patients, and this subset had a more aggressive course with significantly shorter progression‐free survival. In 75% (n = 6/8) of nonresectable patients, we detected potentially actionable alterations. Financial analysis of the global charges, including NGS codes, indicated 63% reimbursement, which is in line with national (U.S.‐based) and international levels of reimbursement. Conclusion Prospective routine clinical genotyping in ACC can identify clinically relevant subsets of patients and is approaching financial sustainability. Demonstrating clinical utility and financial sustainability in an orphan disease (ACC) requires a multiyear and multidimensional program. Implications for Practice Delineation of molecular profiles in adenoid cystic carcinoma (ACC) has been accomplished in the research setting; however, the ability to identify relevant patient subsets in clinical practice has not been assessed. This work presents an approach to perform integrated molecular genotyping of patients with ACC with nonresectable, recurrent, or systemic disease. It was determined that 75% of nonresectable patients harbor potentially actionable alterations and that 63% of charges are reimbursed. This report outlines that orphan diseases such as ACC require a multiyear, multidimensional program to demonstrate utility in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Thierauf

Ramamurthy

et al. 2019

The Oncologist

View full text Add to dashboard Cite

show abstract

“…7 However, solid component is associated with adverse outcome. 8 Necrosis and vascular invasion may not be seen commonly. To highlight epithelial component, immunohistochemical (IHC) markers like CK7 and CAM5.2 may be used while myoepithelail component may be highlighted by SMA and S100 IHC markers.…”

Section: Discussionmentioning

confidence: 99%

Adenoid cystic carcinoma at base of the tongue with rare cervical lymph node metastasis diagnosed on fine needle aspiration cytology

Garg¹,

Gupta

2019

Int J Sci Rep

View full text Add to dashboard Cite

<p>Adenoid cystic carcinoma (ACC) is an uncommon malignant tumour of salivary glands. Occurrence at base of the tongue is rare. Distant metastasis is common, however, metastasis to regional lymph node is not seen commonly, but if occurs carries a bad prognostic value and lessens the average survival age of the patient. Fine needle aspiration cytology (FNAC) in such cases provides early diagnosis for rapid management of the patient. Review of literature shows that very occasional cases are reported with ACC at base of tongue with regional lymph node metastasis. Here, we present such a rare case of a 55 years old male patient with metastatic adenoid cystic carcinoma of cervical lymph node diagnosed on FNAC with primary at base of the tongue.</p>

show abstract

Vascular Endothelial Growth Factor Receptor Inhibitors for Recurrent or Metastatic Adenoid Cystic Carcinoma

Hoff,

Manzi,

Lazar Neto

et al. 2024

JAMA Otolaryngol Head Neck Surg

View full text Add to dashboard Cite

ImportanceThere is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration.ObjectiveTo examine the efficacy, safety, and tolerability of vascular endothelial growth factor receptor (VEGFR) inhibitors in recurrent or metastatic ACC.Data SourcesPubMed, Embase, and Cochrane Library were systematically searched for studies of VEGFR inhibitors in recurrent or metastatic ACC from database inception to August 31, 2023.Study SelectionInclusion criteria were prospective clinical trials of recurrent or metastatic ACC treated with VEGFR inhibitors, reporting at least 1 outcome of interest specifically for ACC. Of 1963 identified studies, 17 (0.9%) met inclusion criteria.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% CIs.Main Outcomes and MeasuresThe primary efficacy outcome was best overall response to VEGFR inhibitors, including objective response, stable disease, or progressive disease (PD). Safety and tolerability outcomes included incidence of grade 3 or higher adverse events, rates of exit from trial due to PD or drug-related toxic effects, and dose reduction rate (DRR).ResultsA total of 17 studies comprising 560 patients with recurrent or metastatic ACC treated with 10 VEGFR inhibitors were included. The objective response rate was 6% (95% CI, 3%-12%; I2 = 71%) and stable disease was the most frequent best overall response (82%; 95% CI, 74%-87%; I2 = 67%). The 6-month disease control (defined as objective response and stable disease) rate was 54% (95% CI, 45%-62%; I2 = 52%). The rate of grade 3 or higher adverse events was 53% (95% CI, 42%-64%; I2 = 81%) and of DRR was 59% (95% CI, 40%-76%). Most patients (57%; 95% CI, 44%-70%; I2 = 83%) continued therapy until PD; 21% (95% CI, 15%-28%; I2 = 62%) of patients suspended therapy for toxic effects. In subgroup analysis by specific VEGFR inhibitor, the objective response rate was 14% (95% CI, 7%-25%; I2 = 0%), stable disease rate was 76% (95% CI, 63%-85%; I2 = 0%), proportion treated until PD was 61% (95% CI, 14%-94%; I2 = 94%), and DRR was 78% (95% CI, 66%-87%; I2 = 39%) with lenvatinib. Corresponding axitinib results were objective response rate of 8% (95% CI, 4%-15%; I2 = 0%) and stable disease rate of 85% (95% CI, 72%-92%; I2 = 69%), with 73% (95% CI, 63%-82%; I2 = 0%) of patients treated until PD, and the DRR was 22% (95% CI, 12%-38%; I2 = 77%). Rivoceranib had the highest objective response rate (24%; 95% CI, 7%-57%) but high heterogeneity among studies (I2 = 95%) and the lowest rate of patients who continued therapy until PD (35%; 95% CI, 20%-55%; I2 = 90%).Conclusions and RelevanceThis systematic review and meta-analysis found that VEGFR inhibitors were associated with high rates of disease stabilization in recurrent or metastatic ACC. Of 10 included VEGFR inhibitors, lenvatinib and axitinib were associated with the best combined and consistent efficacy, safety, and tolerability profiles, substantiating their inclusion in treatment guidelines.

show abstract

Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck

Abstract: Metastatic ACC is not always an indolent disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 456-463, 2017.

Cited by 43 publications

References 33 publications

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Clinically Integrated Molecular Diagnostics in Adenoid Cystic Carcinoma

Adenoid cystic carcinoma at base of the tongue with rare cervical lymph node metastasis diagnosed on fine needle aspiration cytology

Vascular Endothelial Growth Factor Receptor Inhibitors for Recurrent or Metastatic Adenoid Cystic Carcinoma

Contact Info

Product

Resources

About