1. Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas.
- Author
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Das L, Gupta N, Dutta P, Walia R, Vaiphei K, Rai A, Radotra BD, Gupta K, Sreedharanunni S, Ahuja CK, Bhansali A, Tripathi M, Sood R, and Dhandapani S
- Subjects
- Adenoma diagnosis, Adenoma epidemiology, Adenoma pathology, Adult, Cohort Studies, Female, Humans, India epidemiology, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Pituitary Neoplasms diagnosis, Pituitary Neoplasms epidemiology, Pituitary Neoplasms pathology, Prognosis, Retrospective Studies, Treatment Outcome, Adenoma drug therapy, Early Medical Intervention, Pituitary Neoplasms drug therapy, Temozolomide therapeutic use
- Abstract
Introduction: Aggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking., Methods: This was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150-200 mg/m
2 ). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6 -methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h -scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders., Results: The study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6-14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h -scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs . 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h -score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response., Conclusion: Early initiation of TMZ therapy, functional tumors, and low MGMT h -score predict a favorable response to TMZ in APAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Das, Gupta, Dutta, Walia, Vaiphei, Rai, Radotra, Gupta, Sreedharanunni, Ahuja, Bhansali, Tripathi, Sood and Dhandapani.)- Published
- 2021
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