Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma

Abstract

Purpose: To compare the long-term outcomes after intra-arterial cytoreductive chemotherapy (IACC) with conventional treatment for lacrimal gland adenoid cystic carcinoma (ACC).

Design: Retrospective case series.

Participants: Nineteen consecutive patients treated with IACC, followed by orbital exenteration, chemoradiotherapy, and intravenous chemotherapy.

Interventions: Analyses of the histologic characteristics of biopsy specimens, extent of disease at the time of diagnosis, diagnostic surgical procedures, incidence of locoregional recurrences or distant metastases, disease-free survival time, response to IACC, tumor margins at definitive surgery, and toxicity and complications.

Main outcome measures: Disease relapse, disease-free survival, and chemotherapeutic complications.

Results: Eight patients with an intact lacrimal artery had significantly better outcomes for survival (100% vs. 28.6% at 10 years), cause-specific mortality, and recurrences (all P = 0.002, log-rank test) than conventionally treated patients from the University of Miami Miller School of Medicine. These 8 patients (group 1) had cumulative 10-year disease-free survival of 100% compared with 50% for 11 patients (group 2) who had an absence of the lacrimal artery or deviated from the treatment protocol (P = 0.035) and 14.3% for conventionally treated patients (P<0.001). Likewise, group 2 was associated with lower cause-specific mortality than the institutional comparator group (P = 0.038). Prior tumor resection with lateral wall osteotomy, delay in IACC implementation or exenteration, and failure to adhere to protocol are risk factors for suboptimal outcomes.

Conclusions: Neoadjuvant IACC seems to improve overall survival and decrease disease recurrence. An intact lacrimal artery, no disruption of bone barrier or tumor manipulation other than incisional biopsy, and protocol compliance are factors responsible for favorable outcomes. The chemotoxicity complication rate is limited and manageable.

Figure 1. Orbital magnetic resonance imaging (MRI) of a patient with lacrimal gland adenoid cystic carcinoma

1A: Post-resection orbital MRI showing thickening of the left lateral rectus muscle (Arrowhead) and increased soft tissue enhancement of the temporal fossa. (Arrow) 1B: Coronal view showing tumor remnant superior to lateral rectus at orbital apex. (Arrow) 1C: Enlargement of the V₂ segment within the inferior orbital fissure extending to the foramen rotundum, and asymmetrical enlargement of the left cavernous sinus. (Arrow)

Figure 2. Internal carotid artery angiogram, external photograph of the eye, and photomicrograph of a histopathological section of the lacrimal gland from a patient with lacrimal gland adenoid cystic carcinoma

2A: Diagnostic internal carotid artery angiogram showing tumor remnants supplied by the ophthalmic artery. (Arrow) 2B: Skin hyperpigmentation over the medial right brow and forehead. Anterior segment examination showing conjunctival injection, chemosis, hemorrhage, corneal edema, shallow anterior chamber, and hypotony. 2C: Repeat angiogram shows a hypoplastic right ophthalmic artery. (Arrow) Collateral flow from the middle meningeal artery and the distal maxillary artery of the external carotid artery (ECA) is present. 2D: Histopathologic examination of an exenterated specimen shows foci of tumor necrosis and blood vessel thrombosis. H/E 100X.

Figure 3

Kaplan-Meier survival curves irrespective of the cause of death in patients treated for lacrimal gland adenoid cystic carcinoma (ACC). Comparison of survival proportions of patients treated with intraarterial cytoreductive chemotherapy (IACC) as designed, IACC with protocol deviation, historical control that were conventionally treated patients at Bascom Palmer Eye Institute (BPEI), and two case series from the literature.

Figure 4

Kaplan-Meier survival curves of disease specific mortality in patients treated for lacrimal gland adenoid cystic carcinoma (ACC). A comparison of the cumulative Kaplan-Meier survival proportions, when mortality was due to ACC, of patients treated with intraarterial cytoreductive chemotherapy (IACC) as designed, IACC with protocol deviation, historical control conventionally treated patients at Bascom Palmer Eye Institute (BPEI), and one case series from the literature. Deaths unrelated to disease were censored in this analysis.

Figure 5

Kaplan-Meier analysis of recurrences in patients treated for lacrimal gland adenoid cystic carcinoma (ACC). Compares the cumulative Kaplan-Meier proportions of patients without recurrence treated with intraarterial cytoreductive chemotherapy (IACC) as designed, IACC with protocol deviation, and historical control conventionally treated patients at Bascom Palmer Eye Institute (BPEI).