Mota Jose Mauricio, Sousa Luana Guimarães, Braghiroli Maria Ignez, Siqueira Luiz Tenório, Neto João Evangelista Bezerra, Chapchap Paulo, Hoff Ana A de Oliveira, Hoff Paulo M
Instituto do Cancer do Estado de São Paulo, University of Sao Paulo.
Instituto D'Or de Ensino e Pesquisa, Sao Paulo.
Medicine (Baltimore). 2018 Dec;97(52):e13517. doi: 10.1097/MD.0000000000013517.
In the setting of metastatic or locally advanced adrenocortical carcinoma, a limited number of therapies are available and their efficacy is generally below modest. The backbone of treatment remains surgery, even for metastatic disease, whenever it is possible, and mitotane. Chemotherapy can be used with limited results. A small subset of patients with adrenocortical carcinoma may have high mutational burden and harbor mutations in mismatch-repair genes.
We report a 40-year old and a 28-year-old female patients with metastatic adrenocortical carcinoma refractory to multiple treatments.
Next-generation sequencing detected high mutational burden (>10 mutations/megabase) in both patients, one of them with MSH2 mutation.
They were treated with pembrolizumab (100 to 200 mg every 3 weeks).
The patient harboring a MSH2 mutation experienced a long-term complete response after pembrolizumab, while the patient with high mutational burden and absence of mismatch repair deficiency did not have any response.
To the best of our knowledge, this is the first report in the literature of a durable complete response after pembrolizumab in a patient with metastatic adrenocortical carcinoma. Differences in therapy sequencing, possibly abscopal effect related to multiple previous radiotherapy exposition, predictive values of high mutational burden and mutations in mismatch-repair genes are discussed.
在转移性或局部晚期肾上腺皮质癌的情况下，可用的治疗方法有限，其疗效通常不太显著。治疗的主要方法仍然是手术，即使是转移性疾病，只要有可能，以及使用米托坦。化疗的效果有限。一小部分肾上腺皮质癌患者可能具有高突变负荷，并在错配修复基因中存在突变。
我们报告了两名分别为40岁和28岁的女性转移性肾上腺皮质癌患者，她们对多种治疗均耐药。
二代测序检测到两名患者均具有高突变负荷（>10个突变/兆碱基），其中一名患者存在MSH2突变。
她们接受了帕博利珠单抗治疗（每3周100至200毫克）。
携带MSH2突变的患者在接受帕博利珠单抗治疗后获得了长期完全缓解，而高突变负荷且不存在错配修复缺陷的患者没有任何反应。
据我们所知，这是文献中首例关于转移性肾上腺皮质癌患者接受帕博利珠单抗治疗后获得持久完全缓解的报告。文中讨论了治疗顺序的差异、可能与多次既往放疗有关的远隔效应、高突变负荷的预测价值以及错配修复基因中的突变。
