The Multibiomarker Acro-TIME Score Predicts fg-SRLs Response: Preliminary Results of a Retrospective Acromegaly
Sabrina Chiloiro1,2, Rossana Moroni3, Antonella Giampietro1,2
1UOC Endocrinology and Diabetology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 00168 Roma, Italy.
Context:
The prompt control of acromegaly is a primary treatment aim for reducing related disease morbidity and mortality. First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of medical therapies. A non-negligible number of patients do not respond to this treatment. Several predictors of fg-SRL response were identified, but a comprehensive prognostic model is lacking.
Objective:
We aimed to design a prognostic model based on clinical and biochemical parameters, and pathological features, including data on immune tumor microenvironment.
Methods:
A retrospective, monocenter, cohort study was performed on 67 medically naïve patients with acromegaly. Fifteen clinical, pathological, and radiological features were collected and analyzed as independent risk factors of fg-SRLs response, using univariable and multivariable logistic regression analyses. A stepwise selection method was applied to identify the final regression model. A nomogram was then obtained.
Results:
Thirty-seven patients were fg-SRLs responders. An increased risk to poor response to fg-SRLs were observed in somatotropinomas with absent/cytoplasmatic SSTR2 expression (OR 5.493 95% CI 1.19-25.16, P = .028), with low CD68+/CD8+ ratio (OR 1.162, 95% CI 1.01-1.33, P = .032). Radical surgical resection was associated with a low risk of poor fg-SRLs response (OR 0.106, 95% CI 0.025-0.447 P = .002). The nomogram obtained from the stepwise regression model was based on the CD68+/CD8+ ratio, SSTR2 score, and the persistence of postsurgery residual tumor and was able to predict the response to fg-SRLs with good accuracy (area under the curve 0.85).
Conclusion:
Although our predictive model should be validated in prospective studies, our data suggest that this nomogram may represent an easy to use tool for predicting the fg-SRL outcome early.
Insights
A new model predicts acromegaly treatment response in patients receiving first-generation somatostatin receptor ligands (fg-SRLs). Factors like tumor SSTR2 expression and immune cell ratios help predict treatment success for acromegaly patients.
Area of Science:
- Endocrinology
- Oncology
- Immunology
Background:
- Acromegaly management requires effective treatment to reduce morbidity and mortality.
- First-generation somatostatin receptor ligands (fg-SRLs) are standard therapy, but treatment response varies.
- A comprehensive prognostic model is needed to predict fg-SRLs response in acromegaly patients.
Purpose of the Study:
- To develop a prognostic model for predicting fg-SRLs response in acromegaly.
- The model incorporates clinical, biochemical, pathological, and immune tumor microenvironment features.
Main Methods:
- Retrospective monocenter cohort study of 67 treatment-naïve acromegaly patients.
- Analysis of 15 clinical, pathological, and radiological features using logistic regression.
- Development of a predictive nomogram based on significant risk factors.
Main Results:
- Thirty-seven patients (55%) responded to fg-SRLs.
- Predictors of poor response included absent/cytoplasmatic SSTR2 expression and low CD68+/CD8+ ratio.
- Radical surgical resection was associated with a lower risk of poor response.
- The nomogram, using CD68+/CD8+ ratio, SSTR2 score, and residual tumor, achieved an AUC of 0.85 for predicting response.
Conclusions:
- The developed nomogram is a potentially valuable tool for early prediction of fg-SRLs response in acromegaly.
- Further validation in prospective studies is recommended.
- This model may aid in tailoring acromegaly treatment strategies.
