Sun Min-Gwan, Park Sue Jee, Kim Yeong Jin, Moon Kyung-Sub, Kim In-Young, Jung Shin, Oh Hyung-Joo, Oh In-Jae, Jung Tae-Young
Department of Neurosurgery, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 58128, Republic of Korea.
J Clin Med. 2023 Jun 27;12(13):4307. doi: 10.3390/jcm12134307.
There has been controversy over whether to radiologically follow up or use local treatment for asymptomatic small-sized brain metastases from primary lung cancer. For brain tumors without local treatment, we evaluated potential factors related to the brain progression and whether systemic therapy controlled the tumor. We analyzed 96 patients with asymptomatic small-sized metastatic brain tumors from lung cancer. These underwent a radiologic follow-up every 2 or 3 months without local treatment of brain metastases. The pathologies of the tumors were adenocarcinoma ( = 74), squamous cell carcinoma ( = 11), and small cell carcinoma ( = 11). The primary lung cancer was treated with cytotoxic chemotherapy ( = 57) and targeted therapy ( = 39). Patients who received targeted therapy were divided into first generation ( = 23) and second or third generation ( = 16). The progression-free survival (PFS) of brain metastases and the overall survival (OS) of patients were analyzed depending on the age, tumor pathology, number, and location of brain metastases, the extent of other organ metastases, and chemotherapy regimens. The median PFS of brain metastases was 7.4 months (range, 1.1-48.3). Targeted therapy showed statistically significant PFS improvement compared to cytotoxic chemotherapy ( = 0.020). Especially, on univariate and multivariate analyses, the PFS in the second or third generation targeted therapy was more significantly improved compared to cytotoxic chemotherapy (hazard ratio 0.229; 95% confidence interval, 0.082-0.640; = 0.005). The median OS of patients was 13.7 months (range, 2.0-65.0). Univariate and multivariate analyses revealed that the OS of patients was related to other organ metastases except for the brain ( = 0.010 and 0.020, respectively). Three out of 52 patients with brain recurrence showed leptomeningeal dissemination, while the recurrence patterns of brain metastases were mostly local and/or distant metastases (94.2%). Of the 52 patients who relapsed, 25 patients received local brain treatment. There was brain-related mortality in two patients (2.0%). The intracranial anti-tumor effect was superior to cytotoxic chemotherapy in the treatment of asymptomatic small-sized brain metastases with targeted therapy. Consequently, it becomes possible to determine the optimal timing for local brain treatment while conducting radiological follow-up for these tumors, which do not appear to increase brain-related mortality. Furthermore, this approach has the potential to reduce the number of cases requiring brain local treatment.
对于原发性肺癌无症状的小尺寸脑转移瘤，是进行放射学随访还是采用局部治疗一直存在争议。对于未进行局部治疗的脑肿瘤，我们评估了与脑转移进展相关的潜在因素以及全身治疗是否能控制肿瘤。我们分析了96例来自肺癌的无症状小尺寸转移性脑肿瘤患者。这些患者每2或3个月进行一次放射学随访，未对脑转移瘤进行局部治疗。肿瘤的病理类型为腺癌（n = 74）、鳞状细胞癌（n = 11）和小细胞癌（n = 11）。原发性肺癌采用细胞毒性化疗（n = 57）和靶向治疗（n = 39）。接受靶向治疗的患者分为第一代（n = 23）和第二代或第三代（n = 16）。根据年龄、肿瘤病理类型、脑转移瘤的数量和位置、其他器官转移的程度以及化疗方案，分析了脑转移瘤的无进展生存期（PFS）和患者的总生存期（OS）。脑转移瘤的中位PFS为7.4个月（范围1.1 - 48.3个月）。与细胞毒性化疗相比，靶向治疗显示出具有统计学意义的PFS改善（P = 0.020）。特别是，在单因素和多因素分析中，与细胞毒性化疗相比，第二代或第三代靶向治疗的PFS改善更为显著（风险比0.229；95%置信区间，0.082 - 0.640；P = 0.005）。患者的中位OS为13.7个月（范围2.0 - 65.0个月）。单因素和多因素分析显示，患者的OS与除脑以外的其他器官转移相关（分别为P = 0.010和P = 0.020）。52例脑复发患者中有3例出现软脑膜播散，而脑转移瘤的复发模式大多为局部和/或远处转移（94.2%）。在52例复发患者中，25例接受了脑部局部治疗。有2例患者（2.0%）出现与脑相关的死亡。在治疗无症状小尺寸脑转移瘤方面，靶向治疗的颅内抗肿瘤效果优于细胞毒性化疗。因此，在对这些肿瘤进行放射学随访的同时确定脑部局部治疗的最佳时机成为可能，这些肿瘤似乎不会增加与脑相关的死亡率。此外，这种方法有可能减少需要脑部局部治疗的病例数量。
