{"entity":{"id":"adenoid-cystic-carcinoma","kind":"cancer","name":"Adenoid cystic carcinoma","aka":["ACC","Cylindroma (historical)","Adenoid cystic carcinoma of the salivary glands"],"tldr":"Adenoid cystic carcinoma is a slow but relentless cancer of the salivary glands that creeps along nerves and comes back years later, often in the lungs. Surgery with radiotherapy is the only cure, chemotherapy barely works, and the tablets lenvatinib and axitinib can hold spreading disease still for months rather than shrink it.","summary":"Adenoid cystic carcinoma arises in the minor salivary glands of the palate and sinonasal tract, the submandibular gland and the parotid, and occasionally in the lacrimal gland, trachea or breast. It is defined by a MYB-NFIB (or MYBL1) fusion in most cases, grows in cribriform, tubular or solid patterns, and invades nerves, so facial numbness or pain is a common first symptom. A subset with activating NOTCH1 mutations and solid histology behaves aggressively and spreads to bone and liver; the rest progress slowly, with lung metastases that may be watched for years.\n\nCure depends on surgery with the widest margins the anatomy allows, often sacrificing nerves, followed by radiotherapy, which reduces local recurrence but cannot be shown to improve survival in a disease that recurs so late. Unresectable tumours are treated with radiotherapy alone, and heavy-particle therapy has a particular place: the Heidelberg COSMIC trial of intensity-modulated radiotherapy with a carbon-ion boost and the older fast-neutron series reported better local control than photons, and proton and carbon-ion therapy are offered where available.\n\nCytotoxic chemotherapy rarely produces responses. Multikinase inhibitors that block VEGF receptors are the drugs with evidence: lenvatinib produced responses in 15.6 percent of 32 patients with median progression-free survival of 17.5 months in a Memorial Sloan Kettering phase 2, and a randomised phase 2 of axitinib against observation in progressive disease found median progression-free survival of 10.8 against 2.8 months, so both appear in the NCCN guideline for progressive disease while indolent metastases are observed. Immune checkpoint inhibitors have little activity; NOTCH inhibitors gave modest responses in NOTCH1-mutant disease; and the MYB messenger RNA degrader REM-422 and the drug HG146 are in early trials.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Adenoid_cystic_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Adenoid_cystic_carcinoma"}],"tags":["subtype-page","head-and-neck"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tchekmedyian-lenvatinib-adenoid-cystic-jco-2019","paper-persson-myb-nfib-pnas-2009","paper-laurie-licitra-salivary-systemic-jco-2006"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"Rare, but the second commonest salivary gland malignancy; it grows slowly along nerves, recurs years after treatment and spreads to the lungs, so survival keeps falling long after the five-year mark.","subtypes":["Cribriform and tubular pattern (classical, indolent)","Solid pattern or high-grade transformation (aggressive)","NOTCH1-mutant adenoid cystic carcinoma (bone and liver spread, poor outlook)","MYB-NFIB or MYBL1 fusion-positive disease (the majority)","Adenoid cystic carcinoma of the minor salivary glands, palate and sinonasal tract","Adenoid cystic carcinoma outside the head and neck (lacrimal gland, trachea, breast)"],"biomarkers":["MYB immunohistochemistry or MYB-NFIB fusion by FISH or sequencing","NOTCH1 mutation (aggressive subset, NOTCH inhibitor trials)","Perineural invasion and margin status","Solid component and grade","Ki-67","PD-L1 (usually absent)"],"standardOfCare":[{"setting":"Localised, resectable","approach":"Wide resection including involved nerves where needed, with neck dissection for node-positive disease, followed by postoperative radiotherapy to the bed and nerve pathways.","refs":["imrt-igrt","proton-therapy"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Unresectable or inoperable","approach":"Definitive radiotherapy; carbon-ion or proton therapy where available (COSMIC, Heidelberg; fast-neutron series).","refs":["carbon-ion","proton-therapy","imrt-igrt"],"guideline":{"version":"ESMO salivary gland cancer guideline 2022","url":"https://doi.org/10.1016/j.annonc.2022.04.011"}},{"setting":"Slow-growing metastatic disease","approach":"Observation with scans every few months; stereotactic radiotherapy or resection for isolated symptomatic metastases.","refs":["sbrt"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Progressive metastatic disease","approach":"Lenvatinib or axitinib (phase 2 evidence); clinical trials preferred.","refs":["lenvatinib","axitinib","kinase-inhibitors"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Chemotherapy","approach":"Cisplatin with doxorubicin and cyclophosphamide, or single agents, for symptomatic disease after kinase inhibitors; responses are uncommon.","refs":["cisplatin","doxorubicin","cyclophosphamide"],"guideline":{"nccn":"Category 2B","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Trials","approach":"MYB-directed REM-422, HG146 and NOTCH inhibitors for NOTCH1-mutant disease.","refs":["rem-422","nct06118086","nct06781567"]}],"stateOfArt":["Surgery and radiotherapy cure a minority; most patients live with slowly growing metastases for years.","Lenvatinib and axitinib are the first drugs with randomised or reproducible phase 2 evidence of delaying progression.","MYB and NOTCH1 biology has produced the first rational targets and the first trials designed for this disease alone."],"history":[{"year":1859,"title":"Billroth describes the tumour as cylindroma","refs":[]},{"year":2009,"title":"MYB-NFIB fusion identified as the defining genetic event","refs":[]},{"year":2013,"title":"Genomic landscape shows NOTCH1 and chromatin-remodelling mutations","refs":[]},{"year":2019,"title":"Lenvatinib phase 2: median progression-free survival 17.5 months","refs":["lenvatinib"]},{"year":2022,"title":"Randomised phase 2: axitinib delays progression versus observation","refs":["axitinib"]}],"pipeline":["rem-422","nct06118086","nct06781567","lenvatinib","axitinib","carbon-ion"],"openProblems":["No drug shrinks the disease reliably; kinase inhibitors only slow it.","When to start treatment for indolent lung metastases.","Trials are small because the disease is rare and slow.","Perineural spread makes clear margins impossible at the skull base."],"parent":"salivary-gland"},"route":"/cancers/adenoid-cystic-carcinoma/","neighbours":{"paper":[{"id":"paper-tchekmedyian-lenvatinib-adenoid-cystic-jco-2019","kind":"paper","name":"Phase 2 study of lenvatinib in progressive, recurrent or metastatic adenoid cystic carcinoma","route":"/key-papers/paper-tchekmedyian-lenvatinib-adenoid-cystic-jco-2019/"},{"id":"paper-persson-myb-nfib-pnas-2009","kind":"paper","name":"Recurrent fusion of MYB and NFIB transcription factor genes in adenoid cystic carcinoma","route":"/key-papers/paper-persson-myb-nfib-pnas-2009/"},{"id":"paper-laurie-licitra-salivary-systemic-jco-2006","kind":"paper","name":"Systemic therapy in the palliative management of advanced salivary gland cancers (review)","route":"/key-papers/paper-laurie-licitra-salivary-systemic-jco-2006/"}],"drug":[{"id":"axitinib","kind":"drug","name":"Axitinib","route":"/drugs/axitinib/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"rem-422","kind":"drug","name":"REM-422","route":"/drugs/rem-422/"}],"trial":[{"id":"nct06781567","kind":"trial","name":"Clinical Trial of HG146 Administered to Participants with Adenoid Cystic Carcinoma","route":"/trials/nct06781567/"},{"id":"nct06118086","kind":"trial","name":"Study of REM-422 in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma","route":"/trials/nct06118086/"}],"technology":[{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","route":"/technologies/carbon-ion/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"cancer":[{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"}]}}