Practical guideline for recurrent or metastatic adenoid cystic carcinoma
Adenoid cystic carcinoma (ACC) of the parotid gland accounts for approximately 10%–15% of all salivary gland neoplasms and is generally characterized by indolent growth. Conventional ACC is associated with a relatively slow rate of progression, with 5- and 10-year survival rates of approximately 60% and 50%, respectively.
In terms of treatment, R0 resection remains the preferred curative option for treatment-naive patients with resectable ACC. However, due to the intrinsic characteristics of ACC, including perineural invasion, lymph vascular infiltration, and a propensity for distant metastases, a substantial proportion of patients experience disease recurrence despite postoperative adjuvant radiotherapy. Specifically, local recurrence occurs in approximately 40% of cases, and up to 60% of patients develop distant metastases, with the lungs being the most frequent site. Pulmonary metastases from ACC are associated with limited therapeutic options and poor outcomes. Consequently, recurrent/metastatic (R/M) ACC represents a critical unmet clinical need and poses an urgent therapeutic challenge.
Methods
The development of this guideline is based on systematic evidence review, including data from randomized controlled trials (RCTs) and single-arm clinical trials. Given the low incidence of the disease, cohort studies and real-world evidence were also considered. However, case reports and case series were excluded from the evidence base. Levels of evidence and grades of recommendation have been applied using the GRADE system, available at https://doi.org/10.1136/bmj.39489.470347.AD. Statements without grading were considered justified standard clinical practice by the authors.
Recommendations
First-line systemic therapy
A series of studies on single-agent cisplatin chemotherapy have reported objective response rates (ORRs) ranging from 0% to 70%, demonstrating superior overall efficacy compared to other single agents such as mitoxantrone, epirubicin, vinorelbine, paclitaxel, and gemcitabine.
Platinum-based combination therapies, such as cisplatin/vinorelbine (PV), carboplatin/paclitaxel, cisplatin/doxorubicin/cyclophosphamide (CAP), and gemcitabine/carboplatin, have reported ORRs ranging from 0% to 44.4%. Certain chemotherapeutic agents with limited efficacy as monotherapies have shown improved outcomes when combined with platinum-based agents. For instance, the ORR of vinorelbine increased from 15.4% to 44.4% when used in combination with platinum. In addition, CAP is the most extensively studied combination chemotherapy regimen, with ORRs ranging from 25% to 33%. Taken together, combination therapy with either the PV or CAP regimen is recommended as the first-line treatment option.
