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Abstract：
Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.
摘要：
多达80％的免疫检查点抑制剂（ICI）患者面临耐药性。在这种情况下，立体定向消融放疗（SABR）可诱导免疫或外视反应。然而,它的分子决定因素仍然未知。我们提供了一项转化研究的早期结果，该研究评估了在一项前瞻性观察性多中心研究中，从少进展患者的液体活检中对ICI和SABR（I-SABR）联合反应的生物标志物。队列A包括由于临床益处而维持相同ICI且接受伴随SABR的在向ICI的少进展中的转移性患者。B是仅接受SABR的寡转移患者的比较组。在基线(T1)处提取血液样品,在第一个(T2)和最后一个(T3)分数之后，SABR后两个月（T4）和进一步进展（TP）。响应由IRECIST评估并由客观响应率(ORR)-完全和部分响应定义。我们评估外周血单核细胞（PBMC），循环无细胞DNA（cfDNA）和来自细胞外囊泡的小RNA。可以分析27名患者(队列A:n=19;B:n=8)。大多数是患有非小细胞肺癌和一个进展性病变的男性。中位随访时间为6个月，最后一次ORR为63%(26%完全缓解和37%部分缓解).cfDNA从T2到T3的减少与良好的响应相关。在T2时，CD8+PD1+和CD8+PDL1+细胞在无应答者和应答者中增加，分别。在T2,27个微小RNA差异表达。这些是在少进性疾病中响应I-SABR的潜在生物标志物。
