Meedendorp Arenda D, Ter Elst Arja, 't Hart Nils A, Groen Harry J M, Schuuring Ed, van der Wekken Anthonie J
University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Front Oncol. 2018 May 22;8:176. doi: 10.3389/fonc.2018.00176. eCollection 2018.
A 62-year-old man was referred to our university hospital for treatment of advanced adenocarcinoma of the lung after disease progression on two lines of EGFR TKI and one line of chemotherapy. Fluorescent hybridization analysis upon progression showed an amplification. At our weekly Molecular Tumor Board (MTB), a decision was made to treat this patient with afatinib, which resulted in a partial response. However, progression was observed with a facial nerve paresis due to a metastasis in the skull. A biopsy of a location in the thorax revealed the presence of an EGFR-T790M mutation associated with acquired resistance, after which treatment with osimertinib was started. After 6 months, disease progression was observed, and a new biopsy was taken from the pelvic bone, which revealed the original amplification of together with the EGFR-L858R mutation, the EGFR-T790M mutation was not detected. The MTB decided to treat the patient with trastuzumab/paclitaxel. A partial response was observed in different bone lesions, while the skull metastasis with ingrowth in the brain remained stable for 6 months. Because of progression of the bone metastases after 6 months, a biopsy of a lesion in the thorax wall was taken. In this lesion, the EGFR-T790M mutation could be detected again. The MTB advised to start treatment with a combination of osimertinib and afatinib. This resulted in an impressive clinical improvement and a partial response of the bone metastases on the most recent 18-fluorodeoxyglucose positron emission tomography and computer tomography-scan. In conclusion, adjusting treatment to the mutational make-up of the tumor is a great challenge. For optimal treatment response multiple biopsies and re-biopsy upon progression are imperative. As more genes are investigated, treatment decision becomes increasingly difficult, therefore, expert opinions from an MTB is essential.
一名62岁男性在接受两线表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI）和一线化疗后疾病进展，被转诊至我校医院治疗晚期肺癌。病情进展时的荧光杂交分析显示有扩增现象。在我们每周的分子肿瘤委员会（MTB）会议上，决定使用阿法替尼治疗该患者，治疗后出现部分缓解。然而，由于颅骨转移导致面神经麻痹，病情出现进展。对胸部一处病变进行活检，发现存在与获得性耐药相关的EGFR-T790M突变，之后开始使用奥希替尼治疗。6个月后，病情出现进展，遂从骨盆骨取了新的活检样本，结果显示存在最初的扩增现象，同时伴有EGFR-L858R突变，但未检测到EGFR-T790M突变。MTB决定使用曲妥珠单抗/紫杉醇治疗该患者。在不同的骨病变中观察到部分缓解，而脑部有向内生长的颅骨转移灶在6个月内保持稳定。6个月后，由于骨转移灶进展，对胸壁一处病变进行了活检。在该病变中，再次检测到EGFR-T790M突变。MTB建议开始使用奥希替尼和阿法替尼联合治疗。这带来了令人瞩目的临床改善，在最近的18氟脱氧葡萄糖正电子发射断层扫描和计算机断层扫描中，骨转移灶出现部分缓解。总之，根据肿瘤的突变组成调整治疗是一项巨大挑战。为获得最佳治疗反应，在病情进展时进行多次活检和重新活检至关重要。随着更多基因被研究，治疗决策变得越来越困难，因此，MTB的专家意见必不可少。
