MRI T2 signal intensity and tumor response in patients with GH-secreting pituitary macroadenoma: PRIMARYS post hoc analysis

Abstract

Objective Pituitary adenoma MRI T2 signal intensity associates with tumor characteristics including responsiveness to somatostatin analogs (SSAs). These analyses determined whether baseline T2 signal intensity predicts response to primary medical treatment with long-acting SSA. Design Post hoc analyses of the prospective multicenter, open-label, single-arm PRIMARYS study in which patients with treatment-naïve GH-secreting pituitary macroadenomas received fixed-dose lanreotide autogel (120 mg) every 4 weeks for 48 weeks. Methods Associations were investigated between adenoma T2-signal hypo/iso/hyperintensity and treatment responses at week 48/last visit: hormonal control (GH ≤2.5 μg/L and IGF-1 normalization); tumor response (tumor volume reduction (TVR) ≥20%); separate GH/IGF-1 control and change from baseline in GH/IGF-1 and tumor volume. Results Adenomas were hypointense at baseline in 50/85 (59%) patients using visual assessment. Of these, 40% achieved hormonal control and 76% achieved a tumor response. Significant univariate associations arose for hypo- vs isointensity with tumor response and achievement of GH ≤2.5 μg/L, but not IGF-1 normalization or overall hormonal control. In multivariate analysis, tumor response was six times more likely for hypo- vs iso-intense tumors (= 6.15; 95% CI: 1.36–27.88). In univariate change-from-baseline analyses, hypo- vs isointensity was associated with greater TVR and IGF-1 reduction but not change in GH. In multivariate analysis, IGF-1 decreased by an estimated additional 65 μg/L (P = 0.0026)) for hypo- vs isointense. Conclusions Patients with hypointense vs isointense GH-secreting macroadenomas had greater reductions in IGF-1 following primary treatment with lanreotide autogel and were more likely to achieve tumor response. Assessment of T2 signal intensity at baseline may help to predict long-term responses to primary treatment with SSAs.

Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

“…Also, the analysis evaluated only some of the possible predictive factors for response to acromegaly treatment; there are others, such as tumor histopathology (as discussed in the "Introduction") or expression of somatostatin receptors that may also contribute to how patients respond. A recent post hoc analysis of the PRIMARYS data found that IGF-1 levels after treatment with lanreotide autogel were lower in patients with T2-signal hypointense GH-secreting macroadenomas compared with T2-signal isointense GH-secreting macroadenomas, hence assessment of T2-signal intensity was suggested as a predictive factor for long-term response [30]. It should also be noted that the decision to treat with SRLs may not only depend on predictive factors, but also on the cost of medication and availability of experienced surgeons; both of these factors may vary considerably between countries.…”

“…Previous studies have shown that several factors may influence the response to SRLs. These include: age and sex; pre-treatment and early post-treatment TV, GH, and IGF-1 levels; tumor histopathology (Ki-67, somatostatin receptor subtype 2 expression, AIP expression, granularity, β-arrestin expression); imaging characteristics (T2-weighted magnetic resonance imaging signal intensity); genetic factors; and treatment history [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”

A Pituitary Society update to acromegaly management guidelines

“…Older age, female sex, and lower IGF-I levels at baseline were associated with increased probability of achieving long-term biochemical control, but tumor volume response at 12 weeks was not an accurate predictor of subsequent tumor volume control [ 59 ]. Further, patients with a hypointense tumor on T2 MRI showed greater reductions in IGF-I and were more likely to achieve tumor shrinkage [ 60 ]. These results suggest that patient- and tumor-specific factors at baseline may predict long-term biochemical response to primary SRL treatment, while early tumor response may not.…”

T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly

“…T2-weighted MRI signal of the adenoma has been recently recognized as a non-invasive predictor of response to first-generation SRL therapy in acromegaly. Somatotroph adenomas with lower T2-signal intensity are frequently smaller and less invasive than adenomas with a higher T2-signal intensity (9,10,11,12), but the correlation with first-generation SRL-induced tumor shrinkage was inconsistent among studies (9,11,13,14). Although T2-hypointense adenomas are associated with higher GH levels at diagnosis (10), these patients have greater GH and IGF-1 reductions after a median of 6 months of presurgical first-generation SRLs treatment than patients with T2-iso-or T2-hyper-intense adenomas (9,11,14).…”