Dataset Information

Stage and disease-free interval help select patients for surgical management of locally recurrent and metastatic adrenocortical carcinoma.

ABSTRACT:

Background and objectives

Chemotherapeutic options for patients with recurrent/metastatic adrenocortical carcinoma (ACC) are limited, leading to consideration for surgical management. We sought to determine characteristics associated with an unequivocal survival benefit amongst patients undergoing re-resection or metastasectomy.

Methods

Patients who underwent surgery for recurrent/metastatic ACC were identified and stratified into two groups: those with postoperative survival comparable with what has been reported with chemotherapy alone (<12 months) and those surviving twice that duration (>24 months). Those who survived between 12 and 24 months were excluded, as the objective was to characterize patients who most distinctly benefited from resection. Clinicopathologic and treatment variables were evaluated for associations with survival.

Results

Forty-three patients survived more than 24 months and 15 patients died less than 12 months after reoperation. Tumor stage (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45-0.96) and disease-free interval (DFI; OR, 3.23; 95% CI, 1.68-6.22) were associated with prolonged survival. Tumor size, hormonal status, resection margin, and treatment with chemotherapy, radiation, and mitotane were not associated with prolonged survival. Patients who survived more than 24 months underwent more procedures for subsequent recurrences (median 4 vs 2; P < .001).

Conclusion

Stage and DFI can help select optimal candidates for resection of recurrent/metastatic ACC. Patients selected for surgical management should be informed of the likelihood of requiring multiple interventions.

SUBMITTER: Lo W

PROVIDER: S-EPMC8189166 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAdrenocortical carcinoma (ACC) is a rare, often-aggressive neoplasm of the adrenal cortex, with a 14-17 month median overall survival. We asked whether tumors from patients with advanced or metastatic ACC would offer clues as to putative genes that might have critical roles in disease progression or in more aggressive disease biology.MethodsWe conducted comprehensive genomic and expression analyses of ACCs from 43 patients, 30 female, and 42 from metastatic sites, including deep sequencing, copy number analysis, mRNA expression and microRNA arrays.ResultsCopy number gains and losses were similar to that previously reported for ACC. We identified a median mutation rate of 3.38 per megabase (Mb). The mutational signature was characterized by a predominance of C > T, C > A and T > C transitions. Only cancer genes TP53 (26%) and beta-catenin (CTNNB1, 14%) were mutated in more than 10% of samples. The TCGA-identified putative cancer genes MEN1 and PRKAR1A were found in low frequency-4.7 and 2.3%, respectively. The majority of the mutations were in genes not implicated in the etiology or maintenance of cancer. Specifically, amongst the 38 genes that were mutated in more than 9% of samples, only four were represented in Tier 1 of the 576 COSMIC Cancer Gene Census (CCGC). Thus, 82% of genes found to have mutations likely have no role in the etiology or biology of ACC; while the role of the other 18%, if any, remains to be proven. Finally, the transcript length for the 38 most frequently mutated genes in ACC is statistically longer than the average of all coding genes, raising the question of whether transcript length in part determined mutation probability.ConclusionsWe conclude that the mutational and expression profiles of advanced and metastatic tumors are very similar to those from newly diagnosed patients-with very little in the way of genomic aberration to explain differences in biology. With relatively low mutation rates, few major oncogenic drivers, and loss of function mutations in several epigenetic regulators, an epigenetic basis for ACC may be postulated and serve as the basis for future studies.