Schubert Philipp, Rutzner Sandra, Eckstein Markus, Frey Benjamin, Schweizer Claudia, Haderlein Marlen, Lettmaier Sebastian, Semrau Sabine, Gostian Antoniu-Oreste, Zhou Jian-Guo, Gaipl Udo S, Fietkau Rainer, Hecht Markus
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Front Oncol. 2020 Oct 29;10:576643. doi: 10.3389/fonc.2020.576643. eCollection 2020.
BACKGROUND: Local ablative treatments improve survival in patients with oligometastatic disease in addition to chemotherapy. The application of immune checkpoint inhibitors prolonged patients' survival in different tumor entities. This raises the question if patients still benefit from intensified local treatments in combination with a more efficient systemic treatment with immune checkpoint inhibitors. METHODS: The prospective non-interventional ST-ICI trial investigates treatment with PD-1/PD-L1 (Programmed cell death protein 1/Programmed cell death 1 ligand 1) immune checkpoint inhibitors and radiotherapy in different tumor entities. Patients who started radiotherapy and immunotherapy concomitantly were included in this interim analysis. In this cohort patients with all-lesion radiotherapy (all tumor lesions irradiated, al-RT) were compared to patients with radiotherapy to only a single of their tumor lesions (single-lesion radiotherapy, sl-RT). Endpoints of the interim analysis were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). RESULTS: A total of 104 patients were registered between April 2017 and August 2019. Fifty patients started immune checkpoint inhibitor treatment and radiotherapy concomitantly and were included. Most frequent tumor entities were non-small cell lung cancer (62%) followed by head and neck squamous cell cancer (26%). Most frequent location of radiotherapy was lung (34%) and central nervous system (20%). Median duration of follow-up was 8.6 months beginning with first administration of the immune-checkpoint-inhibitor. Median PFS was 9.2 months (95% CI, 5.8 - 12.6) in the al-RT group and 3.0 months (95% CI, 2.5 - 3.5) in the sl-RT group (p<0.001). Median OS was 11.6 months (95% CI, 8.1 - 15.1) in the al-RT group and 4.2 months (95% CI, 3.0 - 5.4) in the sl-RT group (p=0.007). Median TTP was not reached in the al-RT group compared to 4.6 months (95% CI, 1.1-8.0) in the sl-RT group (p=0.028). Univariate Cox regression analyses computed tumor entity, histology, central nervous system metastases, immunotherapy drug and al-RT as predictors of OS (with an effect p-value of ≤ 0.1). In the multivariable analysis only tumor entity and al-RT remained prognostic factors for OS. CONCLUSION: Patients with PD-1/PD-L1 immune checkpoint inhibitor therapy benefit from local radiotherapy to all known lesions compared to single-lesion radiotherapy regarding PFS and OS.
背景：除化疗外，局部消融治疗可提高寡转移疾病患者的生存率。免疫检查点抑制剂的应用延长了不同肿瘤实体患者的生存期。这就提出了一个问题，即患者在联合使用更有效的免疫检查点抑制剂进行全身治疗时，是否仍能从强化局部治疗中获益。 方法：前瞻性非干预性ST-ICI试验研究了PD-1/PD-L1（程序性细胞死亡蛋白1/程序性细胞死亡1配体1）免疫检查点抑制剂与放疗在不同肿瘤实体中的治疗效果。同时开始放疗和免疫治疗的患者纳入本中期分析。在该队列中，将接受全病灶放疗（所有肿瘤病灶均接受照射，al-RT）的患者与仅对单个肿瘤病灶进行放疗（单病灶放疗，sl-RT）的患者进行比较。中期分析的终点为无进展生存期（PFS）、总生存期（OS）和疾病进展时间（TTP）。 结果：2017年4月至2019年8月共登记了104例患者。50例患者同时开始免疫检查点抑制剂治疗和放疗并被纳入研究。最常见的肿瘤实体是非小细胞肺癌（62%），其次是头颈部鳞状细胞癌（26%）。放疗最常见的部位是肺部（34%）和中枢神经系统（20%）。从首次给予免疫检查点抑制剂开始，中位随访时间为8.6个月。al-RT组的中位PFS为9.2个月（95%CI，5.8 - 12.6），sl-RT组为3.0个月（95%CI，2.5 - 3.5）（p<0.001）。al-RT组的中位OS为11.6个月（95%CI，8.1 - 15.1），sl-RT组为4.2个月（95%CI，3.0 - 5.4）（p=0.007）。al-RT组未达到中位TTP，而sl-RT组为4.6个月（95%CI，1.1 - 8.0）（p=0.028）。单变量Cox回归分析将肿瘤实体、组织学、中枢神经系统转移、免疫治疗药物和al-RT作为OS的预测因素（效应p值≤0.1）。多变量分析中，只有肿瘤实体和al-RT仍然是OS的预后因素。 结论：与单病灶放疗相比，接受PD-1/PD-L1免疫检查点抑制剂治疗的患者在PFS和OS方面，从对所有已知病灶进行局部放疗中获益。
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