Adenoid cystic carcinoma

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.

Cure 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.

Cytotoxic 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.