ECE2023 Poster Presentations Pituitary and Neuroendocrinology (123 abstracts)
The acro-TIME score: a new clinical, pathological and immune integrative approach to early identify acromegaly patients resistant to treatment with first generation somatostatin ligands
Sabrina Chiloiro 1,2 , Antonella Giampietro 1,2 , Marco Gessi 3 , Liverana Lauretti 4 , Pierpaolo Mattogno 4 , Flavia Costanza 1,2 , Angela Carlino 3 , Alessandro Olivi 4 , Guido Rindi 3 , Alfredo Pontecorvi 1,2 , Laura De Marinis 1,2 , Francesco Doglietto 4 & Antonio Bianchi 1,2
1Fondazione Policlinico Universitario A. Gemelli, Endocrinology and Diabetology, Rome, Italy; 2Fondazione Policlinico Universitario A. Gemelli, Department of Translational Medicine and Surgery, Rome, Italy; 3Fondazione Policlinico Universitario A. Gemelli, Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Rome, Italy; 4Fondazione Policlinico Universitario A. Gemelli, Neurosurgery, Rome, Italy
Somatotropinomas are benign pituitary tumors, with a heterogenous biological and clinical behavior. Tumor microenvironment reflects the interaction between tumor cells and the host immune system and may regulate tumor behavior and therapy outcome. We develop a scoring system that includes clinical, pathological and immune markers to early identify fg-SRLs resistant acromegaly pts. 43 acromegaly pts were included according the following criteria (1) first line treatment with surgery, (2) post-surgical fg-SRLs therapy (3) availability of tumor sample. Pts not-naïve to acromegaly therapies before surgery, with history of radiotherapy of head/neck within 10 years before pituitary surgery, with immune-related disease were ruled out. Eighteen pts (41.9%) were fg-SRLs resistant: 14 were females (77.8%), with a median age of 36.5 (IQR:13) and with cavernous sinus invasion in 12 cases (66.7%). At histological examination, Ki-67 was <1.5% in 17 cases (39.5%). The SSTR2A Volante scores were 0-1 in 5 cases (11.6%) and 2-3 in 38 cases (88.4%). Tumour-infiltering CD4+ lymphocytes was 4.9/HFP (IQR: 8), CD8+ lymphocytes was 11/HFP (IQR:14) and CD68+ cells was 60/HFP (IQR:69). The ratio CD68+/CD8+ cells was 5.2 (IQR: 5). We analysed 18 clinical, pathological and immune features as possible predictors of fg-SRLs response. Fg-SRLs resistance was associated to age at acromegaly diagnosis <37 years (AUC: 0.72 OR: 2 95%IC: 1.1-4 P=0.04), cavernous sinus invasion (OR: 9.3 95%IC:1.4-61 P<0.001), Ki-67>1.5% (OR: 3.2 95%IC:1.2-13.1 P=0.04), score 0-1 of SSTR2A (OR: 2.7 95%IC: 1.7-4.1 P=0.03), ratio CD68+/CD8+ cells<5.7/HPF (AUC: 0.709 OR: 4.9 95%IC:1.2-19.2 P=0.03) and persistence of post-surgery residual tumour (OR: 2.5 95%IC:1.3-4.7 P=0.004). These variables were analysed in a logistic regression model, yielding a beta coefficient of 3.7 for age >37 years; of -3 for cavernous sinus invasion; of -0.2 for Ki-67>1.5%; of 20 for SSTR2A score 2-3; of -0.9 for CD68+/CD8+cells ratio >5.7/HFP; and of -0.9 for persistence of post-surgery residual. We assigned a score to each covariate proportional to its beta coefficient, yielding a cumulative score for each patient. The score values ranged from 18.5 to 24 in cases responsive to fg-SRLS and from -5.5 to 21.5 in fg-SRLs resistant cases. A score <19 was chosen as cut-point to identify fg-SRLs resistance (AUC: 0.059 P<0.001 95%IC: 0.0-0.126). A score <19 was associated to fg-SRLs resistance in 84.6% of cases (P<0.001 OR: 3.7 95%IC:1.7-6.7). This new score integrates clinical, pathological, immunological data and may predict resistance to fg-SRLs and the need of second line treatments.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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