Predictors of Postoperative Pituitary Adenoma Growth Rate Identified

Researchers identified a variety of patient and tumor-specific characteristics that predict the postoperative growth rate of pituitary adenomas, according to a retrospective review published online ahead of print in the Journal of Clinical Endocrinology and Metabolism.
Process division of cell. Isolated on black background"Currently, the most reliable tool for predicting the growth behavior of pituitary adenomas is to determine the specific histological subtype by utilizing an array of pituitary-specific transcription factors and antibodies against pituitary hormones, explained senior author Gelareh Zadeh, MD, PhD, Assistant Professor of Surgery, University of Toronto, and Scientist, Labatts Brain Tumor Research Centre and Ontario Cancer Research Institute, Toronto, Ontario. "Furthermore, examining the MIB-LI (proliferative index or how fast the cells are dividing) provides an ancillary tool for predicting growth by providing a measure of the proliferative potential of pituitary adenomas. However, to date, the clinical factors that are involved in predicting the growth behavior of pituitary adenoma are not well understood," she said.

"In this study we have examined the association between pre- and postoperative growth characteristics in association to patient demographics, MRI parameters and histopathological factors that may predict growth rate of pituitary adenomas both pre- and postoperatively," Dr. Zadeh said. "This study allows us to establish a more comprehensive clinicopathological framework from which clinicians can make more informed decisions and plan treatment strategies accordingly, and more importantly council patients on the best management options," she added.

The study found that "postoperative growth in cases of incomplete pituitary adenoma removal depends on age, gender, and preoperative growth rate (if those data are available), and less on tumor markers," commented Ferdinand Roelfsema, MD, PhD, Professor in the Department of Endocrinology and Metabolic Diseases at Leiden University Medical Center, Leiden, The Netherlands. "Such data may dictate the frequency for follow-up, although most patients will be under the attendance of endocrinologists, either for the associated persisting hormone overproduction and/or (partial) pituitary insufficiency," Dr. Roelfsema said.

Growth Found in 43% of Residual Pituitary Adenomas
The authors examined clinical and histopathological correlates of growth patterns in 153 patients who underwent resection of pituitary adenomas between 1999 and 2011. After surgery, 34.6% of patients had residual tumors and 43.3% of these tumors grew. The growth rate was calculated as the tumor volume doubling time (TVDT).

Preoperative TVDT was associated with older age (P=0.001), suprasellar tumor extension (P=0.003), cystic or hemorrhagic changes (P=0.004), and the presence of MIB-I LI (P=0.005), FGFR4 positivity (P=0.047), and negativity of p27 (P=0.007). The impact of these predictors varied among the different adenoma types.

Postoperative TVDT was correlated with greater preoperative TVDT (P=0.026), older age (P=0.015), and female gender (P=0.017) in nonfunctioning tumors but not in functioning tumors. Because there were only 6 functioning tumors in this cohort, the authors warned that the findings should be interpreted with caution.

Clinical Implications of the Findings
"For the patient with a functioning pituitary adenoma, postsurgical permanent cure is extremely important," Dr. Roeflsema said. "In about two-thirds of patients this goal can be reached, although the cure rate is lower in patients with nonfunctioning adenomas," he noted citing a study he coauthored.

"The study by Monsalves and colleagues did not investigate the true recurrence rate, but our meta-analysis indicated the lowest recurrence in acromegaly and identical recurrence rates in nonfunctioning adenomas and prolactinoma," Dr. Roelfsema said. "One may assume that a recurrence originates from tiny tumor remnants, not detectable by MRI and sensitive biochemical tools. Interestingly, age, tumor size, tumor extension and sex had no prognostic value on tumor recurrence in our meta-analysis. A low postoperative basal hormone concentration is a prognostically favorable factor. What is clear from this and other studies that there is a real need for nationwide studies that include thousands rather than 100 or 200 patients," he concluded.

"The heterogenity of the clinical manifestations of pituitary adenomas has been an attractive topic for long time, especially the characteristics of recurrent pituitary adenomas," commented Maode Wang, MD, PhD, Director and Professor of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. "Among studies on recurrent or invasive factors, the cytokinetics and oncogenetic studies are the most prevalent in the past decade, such as the research on tumor markers (eg, MIB-1, FGFR4, p27, Ki67 and PCNA) and oncogenes (eg, ras, c-myc, c-fos, p16). However, so far there is no effective means for predicting the growth and recurrent rates of pituitary adenomas," Dr. Wang said.

"Monsalves et al completed a clinical study with large sample size and disclosed that tumor growth rate was relevance to age, gender, tumor growth pattern, presence of cyst/hemorrage, and the expression extent of the MIB-1, FGFR4, P27. We agree with the opinion that postoperative growth rate can be predicted partly by preoperative growth rate, because the tumor occasionally changed its growing properties after operation. In brief, the findings from this study provide valuable information for intensive studies on the recurrent and invasive factors of pituitary adenomas," Dr. Wang said.

Sources
Monsalves E, Larjani S, Loyola Godoy B, et al. Growth patterns of pituitary adenomas and histopathological correlates. J Clin Endocrinol Metab. 2014:jc20133054.

Roelfsema F, Biermasz NR, Pereira AM. Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary. 2012;15(1):71-83. doi: 10.1007/s11102-011-0347-7.

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