Clinical and microdissection genotyping analyses of the effect of intra-arterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.
OBJECTIVE
To determine the effect of intra-arterial cytoreductive chemotherapy (IACC) as an adjunct of a multimodality protocol for the treatment of lacrimal gland adenoid cystic carcinoma (ACC).


METHODS
This was a retrospective, comparative, consecutive case series. Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, local-regional recurrence or distant metastases, and disease-free survival time. Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci using 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serve as markers for the presence of gene deletion. The effect of IACC was assessed by the radiographic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness.


RESULTS
The carcinoma cause-specific death rates between the two treatment groups was significant (P = .029, log-rank test). The cumulative 5-year carcinoma cause-specific death rate was 16.7% in the IACC-treated group compared with 57.1% in the conventional treatment group. 1p36 was the single most common site affected by allelic loss for microsatellite markers in this series.


CONCLUSIONS
The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland ACC. Allelic loss for microsatellite markers at 1p36 may be a common and an early event in ACC formation and progression.
Tse
David T
DT
Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003528:Carcinoma, Adenoid Cystic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D005134:Eye Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D005240:Feasibility Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007269:Injections, Intra-Arterial; D007766:Lacrimal Apparatus Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents