Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Int J Radiat Oncol Biol Phys. 2020 May 1;107(1):62-71. doi: 10.1016/j.ijrobp.2019.12.042. Epub 2020 Jan 25.
Despite the impressive response rate to osimertinib, acquired resistance remains an obstacle to achieving long-term tumor control in metastatic epidermal growth factor receptor-mutant non-small cell lung cancer. Stereotactic body radiation therapy (SBRT) plays a growing role in the management of oligometastatic disease. We investigated the patterns of residual disease and progression on osimertinib, as well as the predictors of candidates for consolidative SBRT.
The serial scans of patients with metastatic epidermal growth factor receptor-mutant non-small cell lung cancer treated with osimertinib were retrospectively reviewed. Disease progression in residual sites, new sites, and both residual and new sites were classified as residual-site recurrence (RR), new-site recurrence (NR), and combined RR and NR (RNR), respectively. Logistic regression analysis was performed to identify predictors of candidates for consolidative SBRT.
Ninety-seven patients were enrolled. The median time to maximal osimertinib response was 2.6 months. Twenty-six patients (26.8%) with oligoresidual disease were identified as candidates for consolidative SBRT at time of maximal response. Stage T1-2 before initiation of osimertinib (P = .046) was the independent predictor of consolidative SBRT eligibility. During a median follow-up of 10.9 months, disease progression was documented in 50 (51.5%) patients, and 70% of them experienced oligoprogression. Twenty-five (50%) patients developed disease progression in originally involved sites, 11 (22%) had new metastases, and 14 (28%) experienced disease progression in both original and new metastatic sites. Forty-six patients had progressive disease after experiencing initial stable disease or objective response to osimertinib. RR occurred in 20 (43.5%) of these patients, NR in 14 (30.4%), and RNR in 12 (26.1%). Notably, within the subgroup of patients eligible for consolidative SBRT, RR was observed in 6 (54.5%) patients, RNR in 3 (27.3%), and NR in 2 (18.2%).
The majority of progressive disease on osimertinib was within residual lesions in initially involved sites. Consolidative SBRT may prolong time to progression in a selected subgroup of patients, which merits further investigation.
尽管奥希替尼的缓解率令人印象深刻，但获得性耐药仍然是转移性表皮生长因子受体突变型非小细胞肺癌实现长期肿瘤控制的障碍。立体定向体部放射治疗（SBRT）在治疗寡转移性疾病方面发挥着越来越重要的作用。我们研究了奥希替尼治疗后残留疾病和进展的模式，以及进行巩固性 SBRT 的候选者的预测因素。
回顾性分析了接受奥希替尼治疗的转移性表皮生长因子受体突变型非小细胞肺癌患者的连续扫描。残留部位、新部位和残留及新部位的疾病进展分别归类为残留部位复发（RR）、新部位复发（NR）和 RR 和 NR 的联合（RNR）。进行逻辑回归分析以确定候选进行巩固性 SBRT 的预测因素。
共纳入 97 例患者。最大奥希替尼反应的中位时间为 2.6 个月。26 例（26.8%）患者在最大反应时被确定为寡残留疾病的候选进行巩固性 SBRT。奥希替尼治疗前 T1-2 期（P =.046）是进行巩固性 SBRT 的独立预测因素。在中位随访 10.9 个月期间，50 例（51.5%）患者出现疾病进展，其中 70%发生寡进展。25 例（50%）患者在最初受累部位出现疾病进展，11 例（22%）出现新转移，14 例（28%）在原始和新转移部位均出现疾病进展。46 例患者在奥希替尼初始稳定疾病或客观缓解后出现疾病进展。在这些患者中，20 例（43.5%）出现 RR，14 例（30.4%）出现 NR，12 例（26.1%）出现 RNR。值得注意的是，在有资格进行巩固性 SBRT 的患者亚组中，6 例（54.5%）出现 RR，3 例（27.3%）出现 RNR，2 例（18.2%）出现 NR。
奥希替尼治疗后进展的大多数疾病位于最初受累部位的残留病变内。在选择的患者亚组中，巩固性 SBRT 可能会延长进展时间，值得进一步研究。
