Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Histopathology, PGIMER, Chandigarh, India.
Front Endocrinol (Lausanne). 2021 Dec 17;12:774686. doi: 10.3389/fendo.2021.774686. eCollection 2021.
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.
This was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150-200 mg/m). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O-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 -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.
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 -scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 . 15 months, = 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 -score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.
Early initiation of TMZ therapy, functional tumors, and low MGMT -score predict a favorable response to TMZ in APAs.
侵袭性垂体腺瘤（APAs）根据定义对最佳多模式治疗具有抗性。挑战在于早期识别和及时管理。替莫唑胺（TMZ）在 APAs 患者中的应用越来越多，但缺乏早期起始时具有良好反应的证据。
这是一项对所有接受至少 3 个 TMZ 周期（150-200mg/m）治疗的 APA 患者的单中心研究。记录了他们的基线临床生物化学和影像学特征。对细胞周期标志物 O-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）、MutS 同源物 2（MSH2）、MutS 同源物 6（MSH6）、MutL 同源物 1（MLH1）和减数分裂后分离增加 2（PMS2）进行免疫组织化学评估，并计算 -分数（阳性细胞数和染色强度的乘积）。根据 RECIST 标准评估影像学反应来评估反应。疾病得到控制（肿瘤体积减少≥30%）的患者被归类为应答者。
该研究包括 35 名患者（48.6%肢端肥大症，37.1%催乳素瘤，14.3%无功能垂体腺瘤）。TMZ 周期中位数为 9（IQR 6-14）。应答者占队列的 68.6%，更有可能患有功能性肿瘤，MGMT 阳性染色细胞的比例较低，MGMT -分数较低。与应答者相比，非应答者 TMZ 治疗开始的潜伏期明显更长（中位数 36.15 个月，=0.01）。从诊断到 TMZ 开始的时间间隔、低至中等 MGMT 阳性（40%肿瘤细胞）和 MGMT -评分 80 的 ROC 衍生截断值均具有超过 80%的敏感性和超过 70%的特异性，可预测反应。
APAs 中 TMZ 治疗的早期开始、功能性肿瘤和低 MGMT -评分预测对 TMZ 有良好的反应。
