Endocrine Abstracts

JOINT343

Among monohormonal densely&sparsely granulated somatotrophic tumors (DGSTs&SGSTs), SGSTs are more difficult to treat, as they are marked by invasive growth, recurrent course and refractoriness to drug therapy (DT) with fg-SRLs. Prioritized and undifferentiated use of fg-SRLs without considering ST receptor status inevitably leads to low efficacy of DT and negative life prognosis of patients with SGSTs.

Aim of this study: To investigate the reasons for low efficacy of fg-SRLs monotherapy and efficacy of combined administration of fg-SRLs&pegvisomant (PEG) for achieving acromegaly control.

Materials and methods: We retrospectively analyzed the efficacy of secondary DT of fg-SRLs in 62 acromegaly patients with a verified morphologic diagnosis who received prolonged forms of octreotide (20-30mg/28days) and lanreotide (120mg/28-56days). Based on final IGF-1 index (II) value, all patients were divided into 2 groups with II <1 [group 1(30 patients)] and >1 [group 2(32 patients)].

Results: In both groups patients did not differ in age of diagnosis [42.2±12.2 vs. 41.0±11.2 years(P = 0.68)] and duration of treatment [31.1±20.1 vs. 31.5±19.0 months(P = 0.9)]. In group 2 (resistant) patients had larger baseline II [3.1±0.9 vs. 2.4±0.8(P = 0.0025)], larger residual tumor volume [1.9±3.4 vs. 0.5±1.3cm³(P = 0.0391)] and higher final II [1.7±0.6 vs. 0.8±0.2(P <0.0001)] compared to group 1. Low percentage of IGF-1 level reduction after 3-6 months of treatment in patients of group 2 [28.2±22.0&26.6±23.0% vs. 57.0±22.6&61.3±20.7%(P <0.0001)] is also different compared to patients of group 1, which indicates key importance of STs selective receptor sensitivity factor to fg-SRLs. In group 2 immunohistochemical analysis revealed high presence of patients with SGSTs [72%(23) vs. 37%(11); P = 0.0075], lower SSTR2 expression [7.1±4.0 vs. 9.1±3.7 scores(IRS); P = 0.0479], lower SSTR2/SSTR5 ratio [1.5±1.2 vs. 3.4±3.1(P = 0.0025)] and higher proportion of cells with fibrous bodies [2.6±0.8 vs. 2.1±0.9 scores(P = 0.024)] compared to group 1. Regarding cellular composition of STs, tumors from chromophobic cells were predominant in group 2 [69%(22) vs. 23%(7); P = 0.0006], tumors from intermediate-type cells were observed less frequently [25%(8) vs. 50%(15); P = 0.046] and tumors from eosinophilic cells were even less frequent [6%(2) vs. 27%(8); P = 0.0285] compared to group 1. To control acromegaly, patients in the resistant group were treated with combined therapy of fg-SRLs&PEG (18.4±8.8mg/day) for 6-55 months, as a result of which 73% of patients achieved biochemical remission in the absence of significant adverse events. The final II value decreased from 1.7±0.6 to 0.97±0.4(P <0.0001).

Conclusions: 1. Among the reasons for insufficient efficacy of fg-SRLs monotherapy high secretory activity, specificity of cellular composition of STs and low SSTR2 expression should be emphasized. 2. Combined use of fg-SRLs&PEG in refractoriness to fg-SRLs monotherapy contributes to achievement of biochemical remission in 73% of cases.