Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas.
Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas.
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DOI：
10.3389/fendo.2021.774686
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发表时间：
2021
影响因子：
5.2
通讯作者：
Dhandapani S
中科院分区：
文献类型：
--
作者：
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;Dhandapani S
侵袭性垂体腺瘤（APA），根据定义，抵抗最佳的综合治疗。挑战在于及早发现和及时管理这些问题。替莫唑胺越来越多地用于APA患者，但缺乏证据支持早期启动的有利反应。这是一项在接受至少3个周期替莫唑胺（150-200 mg/m2）治疗的所有APA患者中进行的单中心研究。记录他们的基线临床生化和放射学特征。对细胞周期标志物O 6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）、MutS同源物2（MSH 2）、MutS同源物6（MSH 6）、MutL同源物1（MLH 1）和减数分裂后分离增加2（PMS 2）进行免疫组织化学评价，并计算h评分（阳性细胞数和染色强度的乘积）。使用RECIST标准评估放射学缓解。疾病得到控制（肿瘤体积缩小≥30%）的患者被归类为应答者。该研究包括35例患者（48.6%肢端肥大症，37.1%泌乳素瘤和14.3%无功能垂体腺瘤）。替莫唑胺（TMZ）周期的中位数为9（IQR 6-14）。应答者占队列的68.6%，更可能患有功能性肿瘤，MGMT阳性染色细胞的百分比较低，MGMT h评分较低。与应答者相比，无应答者开始TMZ治疗的滞后期显著更长（中位36个月vs. 15个月，p = 0.01）。ROC衍生的诊断和TMZ治疗之间的截止时间为31个月，低至中等MGMT阳性（40%肿瘤细胞）和MGMT h评分为80，预测缓解的灵敏度超过80%，特异性超过70%。早期开始TMZ治疗、功能性肿瘤和低MGMT h评分可预测APA患者对TMZ的良好反应。
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/m2). 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. 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. Early initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.
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影响因子：
1.9
作者：
Dhandapani, Sivashanmugam;Narayanan, Rajasekhar;Gupta, Sunil K.
通讯作者：
Gupta, Sunil K.
影响因子：
2.8
作者：
Patil, Ninad R.;Dhandapani, Sivashanmugam;Gupta, Sunil K.
通讯作者：
Gupta, Sunil K.
影响因子：
3.9
作者：
Cros, J.;Hentic, O.;Couvelard, A.
通讯作者：
Couvelard, A.
影响因子：
4.7
作者：
Fisher JP;Adamson DC
通讯作者：
Adamson DC
影响因子：
12.7
作者：
Trouillas, Jacqueline;Roy, Pascal;Raverot, Gerald
通讯作者：
Raverot, Gerald