The Effect Of Long-acting Somatostatin Analogs On Radiotherapy In Acromegalic Patients

Ojective:To explore the effect of long-acting somatostatin analogs(SSA)on the efficacy and safety of radiotherapy in acromegalic patients.Methods:1.Study population:acromegalic patients who received fractionated radiotherapy(FRT)in our center from Jan 2004 to Dec 2020 were included in this study.Additional restrictions were age? 18 years old at the time of radiotherapy and SSA prescription in the medical records.Minimal follow-up requirement was 3 months.Patients with radiosurgery history were excluded.Patients with dopamine agonists usage within 2 months before radiotherapy or continuous usage over 6 months after radiotherapy were also excluded.2.Grouping:patients were divided into 4 groups according to SSA usage before and after radiotherapy:SSA-FRT,FRT,SSA-FRT-SSA and FRT-SSA.SSA pretreatment was defined as Sandostatin 20 mg within 3 months or Somatuline 40 mg within 1 month before radiotherapy.Post-radiotherapy SSA users included anyone with SSA prescription after radiotherapy.3.Information collecting:Baseline and post-radiotherapy follow-up history,laboratory tests,pituitary imaging,pathology and treatment information were collected for each group.4.Statistical analysis:compare laboratory results between the SSA-FRT and FRT groups,including the percentages to the baseline levels of growth hormone(GH%),GH nadir in the oral glucose tolerance test for GH(GH nadir%),and sex-and age-adjusted insulin-like growth factor 1 standard deviation scores(IGF-1 SDS%)at multiple time points after radiotherapy,as well as differences in biochemical remission rates between this two groups;compare differences in biochemical control rates between the SSA-FRT-SSA and FRT-SSA groups;compare the baseline PRL,highest PRL after radiotherapy and the proportion meeting the diagnostic criteria of high PRL between the four groups.Results:1.GH%at 3 months after radiotherapy was significantly higher in the SSA-FRT group(101.49±42.10%,n=8)than in the FRT group(69.53±30.81%,n=21,P=0.032),and the proportion of patients with further elevated GH in the SSA-FRT(50.00%)was also higher than the FRT group(14.29%).Logistic multifactorial regression models suggested that SSA use prior to radiotherapy was the risk factor for this phenomenon.There was a trend of higher GH%in the SSA-FRT group than in the FRT group at other time points,but none of them reached statistical significance.2.No significant difference was found in GH-nadir%and IGF-1 SDS%between the SSA-FRT group and the FRT group during 3 years of follow-up after radiotherapy.3.No significant difference in remission rates was found between the SSA-FRT and the FRT group under different biochemical remission criteria.4.No significant difference in biochemical control rates was found between the SSA-FRT-SSA and the FRT-SSA group.However,the FRT-SSA group tolerated longer SSA injection intervals(medial interval:7 weeks)than the SSA-FRT-SSA group(medial interval:4 weeks,P=0.017)to maintain biochemical control 2 years after radiotherapy.5.Compared with FRT,no significant difference was found in the occurrence of deficiency in HPA,HPT and HPG axis for the SSA-FRT,FRT-SSA and SSA-FRT-SSA groups,respectively.6.No significant difference was found in the baseline PRL,highest post-radiotherapy PRL level and the proportion meeting the diagnostic criteria of hyperprolactinemia between the four groups.Conclusions:1.The usage of SSA prior to pituitary radiotherapy in acromegalic patients resulted in a slower decline in GH in the short term after radiotherapy,but had no significant effect on the long-term biochemical remission.2.The usage of SSA before and after radiotherapy in acromegalic patients did not serve as radioprotector or radiation mitigator for the hypothalamus and anterior pituitary regarding their function of hormone secretion.