The best magazine
Predictors of Biochemical Control
The selection of patients for treatment with SSAs has changed over time. A report by Bevan et al. in 2002 suggested that the control of GH and IGF-I was unlikely in patients with a GH level > 20 ng/ml and an IGF-I level > 900 ng/ml. On the other hand, in 2006 Cozzi et al. showed in 110 patients treated with octreotide LAR that the untreated IGF-I concentration, whether very high or low, did not predict response. Furthermore, in a 2010 report by Melmed et al., patients with less severe acromegaly at baseline had better responses to treatment with lanreotide. No reliable predictive factors relating to a final dose frequency were identified in any studies, and thus stressing the importance of individual tailoring of the dosing regimen for each patient.
Tumor Shrinkage
A number of studies have reported tumor shrinkage in patients with acromegaly treated with SSA therapy, both adjunctively and primarily. This shrinkage can be significant (20%–80% in about one-third of patients) but unpredictable (Fig. 2).
(Enlarge Image)
Figure 2.
Coronal post-Gd T1-weighted MR images obtained in a 31-year-old woman with a GH-secreting pituitary adenoma. She underwent partial tumor resection due to cavernous sinus involvement. A: Preoperative. B: Three months postoperative. C: Six months after starting SSA. D: One year post-SSA treatment.
Tumor reenlargement after SSA discontinuation has also been noted in some cases. Several mechanisms have been proposed for the observed reversible tumor shrinkage; however, the exact cellular mechanism remains unclear.
Primary therapy, as expected, has more impressive shrinkage results. In a prospective study in 99 patients with acromegaly, 75.5% experienced ≥ 25% tumor shrinkage after 12 months, while a significant increase in tumor mass occurred in only 2.1% of the patients. The best predictor of tumor shrinkage was posttreatment IGF-I levels, with patients having the lowest IGF-I level also demonstrating the best tumor shrinkage. A longer prospective study confirmed this observation; the higher the basal GH values and the greater the GH/IGF-I changes, the greater the tumor shrinkage. The authors reported tumor shrinkage of 62% ± 31% (range 0%–100%) in 82.1% of patients.
Use of SSAs in Primary Therapy
Somatostatin analogs may be equally effective if used as adjuvant or initial therapy. Most studies examining the efficacy of long-acting SSAs have focused on patients after surgery and radiation treatment. More recently, however, a large cohort of patients has been treated with primary/de novo therapy. For microadenoma cases in which the surgical cure rate can reach 80%–90%, primary SSA therapy should be used only in those patients who refuse to undergo or have contraindications for surgery. At this time, there are no randomized controlled studies that compare primary medical therapy with initial surgery.
A large German study, Acrostud y 2008, showed that pituitary surgery in 554 patients normalized GH and IGF-I levels in 54.3% and 67.2% of patients, respectively. This approach was clearly more effective than the 36.3% (normalized GH) and 30.5% (normalized IGF-I) obtained by using primary SSA in 145 patients. In some of the SSA-treated patients, the control rate increased slightly with a longer administration of medical therapy (> 360 days).
In a recently published 5-year primary SSA trial by Colao et al., differing results were achieved. In all 45 patients on prolonged octreotide LAR therapy (28 patients) and lanreotide therapy (17 patients), successful control of GH and IGF-I was achieved, and hypertension, cardiac function, and lipid abnormalities improved. Interestingly, glucose metabolism was not affected despite biochemical control. Unfortunately, these data represent only those patients who were fully responsive to SSA, as another 31 patients unresponsive to SSA therapy underwent surgery within 1–2 years.
Overall, we conclude that SSAs are a good primary treatment option in carefully selected patients.
Pretreatment with SSAs
It has been suggested that SSA treatment prior to surgery can reduce surgical risks and potentially improve surgical cure results. While symptomatic improvement and reduction in soft tissue swelling have been well documented, the effect of SSA pretreatment on surgical outcome remains unclear at present. In the ACROSTUDY 2008, for example, SSA treatment before surgery was shown to improve surgical outcome only marginally.
One of a few well-designed prospective studies by Carlsen et al. suggested that with pituitary macroadenomas, SSA pretreatment improves surgical outcomes; however, the surgical cure rate (23% achieved IGF-I normalization, and just 16% by using a combined criteria, that is, adding a GH nadir during OGTT ≤ 1.0 ng/L) was much lower than the average reported in the literature (between 50% and 70%). Most probably, the relatively low cure rate combined with just the few microadenomas included in the study played a role in the negative effects of pretreatment in pituitary microadenomas. Interestingly, in contrast with other studies, Carlsen et al. noted that SSA pretreatment increased the consistency of the tumor, making the tumor more fibrotic and easier to identify during surgery.
Source: ...