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RET融合基因阳性肺癌:14例病例系列的治疗反应及临床特征

RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients.

作者信息

Sarfaty Michal, Moore Assaf, Neiman Victoria, Dudnik Elizabeth, Ilouze Maya, Gottfried Maya, Katznelson Rivka, Nechushtan Hovav, Sorotsky Hadas Gantz, Paz Keren, Katz Amanda, Saute Milton, Wolner Mira, Moskovitz Mor, Miller Vincent, Elvin Julia, Lipson Doron, Ali Siraj, Gutman Lior Soussan, Dvir Addie, Gordon Noa, Peled Nir

机构信息

Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.

出版信息

Clin Lung Cancer. 2017 Jul;18(4):e223-e232. doi: 10.1016/j.cllc.2016.09.003. Epub 2016 Oct 29.

DOI:10.1016/j.cllc.2016.09.003
PMID:28082048
Abstract

BACKGROUND

RET (rearranged during transfection) fusions have been reported in 1% to 2% of lung adenocarcinoma (LADC) cases. In contrast, KIF5B-RET and CCDC6-RET fusion genes have been identified in 70% to 90% and 10% to 25% of tumors, respectively. The natural history and management of RET-rearranged LADC are still being delineated.

MATERIALS AND METHODS

We present a series of 14 patients with RET-rearranged LADC. The response to therapy was assessed by the clinical response and an avatar model in 2 cases. Patients underwent chemotherapy, targeted therapy, and immunotherapy.

RESULTS

A total of 14 patients (8 women; 10 never smokers; 4 light smokers; mean age, 57 years) were included. KIF5B-RET and CCDC6-RET variants were diagnosed in 10 and 4 cases, respectively. Eight patients had an early disseminated manifestation, seven with KIF5B-RET rearranged tumor. The features of this subset included bilateral miliary lung metastases, bone metastases, and unusual early visceral abdominal involvement. One such patient demonstrated an early and durable complete response to cabozantinib for 7 months. Another 2 patients treated with cabozantinib experienced a partial response, with rapid significant clinical improvement. Four patients with tumors harboring CCDC6-RET and KIF5B-RET fusions showed pronounced and durable responses to platinum-based chemotherapy that lasted for 8 to 15 months. Two patients' tumors showed programmed cell death ligand 1-positive staining but did not respond to pembrolizumab. The median overall survival was 22.8 months.

CONCLUSION

RET-rearranged LADC in our series tended to occur as bilateral disease with early visceral involvement, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response. However, further studies are required in this group of patients.

摘要

背景

在1%至2%的肺腺癌(LADC)病例中报道过RET(转染期间重排)融合。相比之下,分别在70%至90%和10%至25%的肿瘤中鉴定出KIF5B-RET和CCDC6-RET融合基因。RET重排的LADC的自然病史和治疗方法仍在探索中。

材料与方法

我们报告了一系列14例RET重排的LADC患者。通过临床反应和2例患者的虚拟模型评估治疗反应。患者接受了化疗、靶向治疗和免疫治疗。

结果

共纳入14例患者(8例女性;10例从不吸烟者;4例轻度吸烟者;平均年龄57岁)。分别在10例和4例中诊断出KIF5B-RET和CCDC6-RET变异。8例患者有早期播散表现,7例为KIF5B-RET重排肿瘤。该亚组的特征包括双侧粟粒性肺转移、骨转移和不寻常的早期腹部内脏受累。其中1例患者对卡博替尼表现出早期且持久的完全缓解,持续7个月。另外2例接受卡博替尼治疗的患者出现部分缓解,临床有快速显著改善。4例携带CCDC6-RET和KIF5B-RET融合的肿瘤患者对铂类化疗表现出显著且持久的反应,持续8至15个月。2例患者的肿瘤显示程序性细胞死亡配体1阳性染色,但对派姆单抗无反应。中位总生存期为22.8个月。

结论

我们系列中的RET重排LADC倾向于表现为双侧疾病并伴有早期内脏受累,尤其是KIF5B融合。卡博替尼治疗取得了反应,包括1例完全缓解。然而,该组患者还需要进一步研究。

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