Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Anticancer Res. 2013 Dec;33(12):5597-602.
BACKGROUND/AIM: We have previously reported that low expression of excision repair cross-complementing-1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase-M1 (RRM1) is indicative of a favorable prognosis in patients with c-N2,3 non-small cell lung cancer (NSCLC) treated with surgery after induction chemoradiotherapy. In the present study, we prospectively explored the tailor-made treatment menu for induction chemotherapy according to the status of biomarkers, and evaluated the biomarker status pre- and post-chemotherapy.
Twenty-five patients with pathologically-proven NSCLC who were not appropriate candidates for initial surgery were enrolled (October 2010 to June 2012, stage IIIA/B/IV1a/1b;14/5/2/4 respectively). Immunohistochemistry was performed to evaluate intratumoral expression of biomarkers. Epidermal growth factor receptor (EGFR) mutation was evaluated by direct sequencing. Two to four cycles of chemotherapy were performed with or without concurrent radiation (50 Gy).
Docetaxel (n=12), pemetrexed (n=4), S-1 (n=4), docetaxel-plus-bevacizumab (n=3), and pemetrexed-plus-bevacizumab (n=2), in combination with platinum were selected for the therapeutic regimen. Twenty-one (84.0%) patients exhibited good partial response, and underwent complete resection without major morbidity or mortality. Of these 21 patients, four achieved a pathologically-complete response (PCR), and 10 achieved a major pathological response. The 3-year overall survival rate was 58.7% for the 25 patients overall, and the 2-year overall survival rate was 73.6% for patients who underwent surgery. Among the 17 patients who underwent resection (except for four with PCR), the status of ERCC1, tubulin, TYMS, RRM1 and EGFR changed markedly after chemotherapy in six patients, eleven patients, eight patients, nine patients and one patient, respectively.
Chemotherapy followed by surgery on the basis of biomarker examination is a challenging approach for patients with advanced NSCLC who otherwise have poor outcomes. Post-chemotherapy biomarker status changed markedly in many cases.
背景/目的：我们之前曾报道，在接受诱导放化疗后行手术治疗的 c-N2,3 非小细胞肺癌（NSCLC）患者中，低表达切除修复交叉互补基因 1（ERCC1）、III 类β-微管蛋白（微管蛋白）、胸苷酸合成酶（TYMS）和核糖核苷酸还原酶-M1（RRM1）预示着较好的预后。在本研究中，我们前瞻性地根据生物标志物状态探索了诱导化疗的个体化治疗方案，并评估了化疗前后的生物标志物状态。
共纳入 25 例经病理证实的 NSCLC 患者（2010 年 10 月至 2012 年 6 月，III A/B/IV1a/1b 期；分别为 14/5/2/4 例），这些患者不适合初始手术。采用免疫组织化学法检测肿瘤内生物标志物的表达情况。采用直接测序法检测表皮生长因子受体（EGFR）突变。行 2-4 个周期的化疗，联合或不联合放疗（50 Gy）。
25 例患者分别选择多西他赛（n=12）、培美曲塞（n=4）、替吉奥（n=4）、多西他赛联合贝伐珠单抗（n=3）和培美曲塞联合贝伐珠单抗（n=2）联合铂类药物进行治疗。21 例（84.0%）患者部分缓解良好，并在无重大并发症或死亡率的情况下接受了完全切除术。这 21 例患者中，4 例获得完全病理缓解（PCR），10 例获得主要病理缓解。25 例患者的 3 年总生存率为 58.7%，行手术的患者 2 年总生存率为 73.6%。在 17 例行切除术的患者中（除 4 例 PCR 患者外），6 例、11 例、8 例、9 例和 1 例患者的 ERCC1、微管蛋白、TYMS、RRM1 和 EGFR 状态在化疗后发生明显变化。
对于那些预后较差的晚期 NSCLC 患者，在生物标志物检测的基础上进行化疗后行手术是一种具有挑战性的方法。许多情况下，化疗后生物标志物状态发生显著变化。
