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接受抗PD-1治疗的患者中椎体转移和转移性脊髓压迫的姑息性放射治疗

Palliative Radiation Therapy for Vertebral Metastases and Metastatic Cord Compression in Patients Treated With Anti-PD-1 Therapy.

作者信息

Fareed Muhammad Mohsin, Pike Luke R G, Bang Andrew, Huynh Mai Anh, Taylor Allison, Spektor Alexander, Awad Mark M, Ott Patrick A, Krishnan Monica, Balboni Tracy A, Schoenfeld Jonathan D

机构信息

Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, ON, United States.

出版信息

Front Oncol. 2019 Mar 29;9:199. doi: 10.3389/fonc.2019.00199. eCollection 2019.

Abstract

There is increasing use of immune checkpoint blockade (ICB) across multiple cancer types, including in patients at risk for vertebral metastases and cord compression. These patients are often treated with palliative radiotherapy (PRT); however, data evaluating the combination of PRT and ICB in patients with vertebral metastases is limited. Furthermore, patients with cord compression are generally excluded from prospective clinical trials. Therefore, we retrospectively evaluated outcomes following PRT and PD-1 inhibition in patients with vertebral metastases. We performed a retrospective chart review of 37 consecutive patients (total 57 lesions) treated with radiation for vertebral metastases who also received PD-1 inhibition. Patient, treatment and outcomes data were abstracted from the medical records. Histologies included non-small cell lung cancer ( = 21), renal cell carcinoma ( = 9) and melanoma ( = 7). Out of 57 lesions,18 involved >1 segments of the vertebral column. There were isolated lesions in thoracic (16), lumbar (9), cervical (6), and sacral (8) vertebrae. Presenting symptoms included pain (19), numbness (10), and weakness (3). Eleven patients were asymptomatic. Radiologic cord compression was present in 12, epidural extension in 28 and compression fracture in 14. Eleven patients underwent surgical decompression prior to the onset of RT. Median radiation dose was 24 Gy (range 8-30 Gy). Stereotactic radiation was delivered in 4 patients; 33 patients received conformal RT. 21 patients received PD-1 inhibition after RT, 9 before RT and 7 with RT. Seven patients received concurrent CTLA-4 inhibitors with anti-PD-1 therapy. Treatment was in general well-tolerated. Toxicities included fatigue (6), transient pain flare (1), nausea/vomiting (1) and G1 skin changes (1). All patients reported some degree of pain relief. Numbness/weakness was improved in 6 of 13 patients with baseline symptoms (46%) and this was more likely in patients that received vertebral radiation after starting PD-1 inhibitors (71 vs. 17%, = 0.04). Most patients (22 of 33 evaluable patients, 67%) had stability of irradiated lesions on subsequent follow up imaging performed at median of 30 days from RT, whereas 3 had a complete local response and 4 had a partial local response. We demonstrate that PRT administered to vertebral metastases was well-tolerated and effective in patients treated with PD-1 inhibitors. There was an encouraging rate of pain reduction and neurological improvement.

摘要

免疫检查点阻断(ICB)在多种癌症类型中的应用日益增加,包括有椎体转移和脊髓压迫风险的患者。这些患者通常接受姑息性放疗(PRT);然而,评估PRT与ICB联合用于椎体转移患者的数据有限。此外,脊髓压迫患者通常被排除在前瞻性临床试验之外。因此,我们回顾性评估了PRT和PD-1抑制治疗椎体转移患者的疗效。我们对37例连续接受椎体转移放疗且同时接受PD-1抑制治疗的患者(共57个病灶)进行了回顾性病历审查。患者、治疗及疗效数据均从病历中提取。组织学类型包括非小细胞肺癌(=21)、肾细胞癌(=9)和黑色素瘤(=7)。在57个病灶中,18个累及>1个椎体节段。胸椎(16个)、腰椎(9个)、颈椎(6个)和骶椎(8个)均有孤立病灶。出现的症状包括疼痛(19例)、麻木(10例)和无力(3例)。11例患者无症状。12例存在放射学脊髓压迫,28例有硬膜外扩展,14例有压缩性骨折。11例患者在放疗开始前接受了手术减压。中位放疗剂量为24 Gy(范围8 - 30 Gy)。4例患者接受了立体定向放疗;33例患者接受了适形放疗。21例患者在放疗后接受PD-1抑制治疗,9例在放疗前接受,7例在放疗期间接受。7例患者在接受抗PD-1治疗的同时接受了CTLA-4抑制剂治疗。治疗总体耐受性良好。毒性反应包括疲劳(6例)、短暂性疼痛加剧(1例)、恶心/呕吐(1例)和1级皮肤改变(1例)。所有患者均报告有一定程度的疼痛缓解。13例有基线症状的患者中,6例(46%)的麻木/无力症状得到改善,且在开始PD-1抑制剂治疗后接受椎体放疗的患者中更可能出现这种情况(71%对17%,=0.04)。大多数患者(33例可评估患者中的22例,67%)在放疗后中位30天进行的后续随访影像学检查中,照射病灶保持稳定,而3例有完全局部缓解,4例有部分局部缓解。我们证明,对椎体转移患者进行PRT,在接受PD-1抑制剂治疗的患者中耐受性良好且有效。疼痛减轻和神经功能改善的比例令人鼓舞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4948/6450051/8eec9fb404cf/fonc-09-00199-g0001.jpg

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